Cardiology free book TABLE OF CONTENTS ( Click on the title of each chapter to see the selected chapter)

Cardiology free e-book online 

TABLE OF CONTENTS ( Click on the title of each chapter to see the selected chapter)

The Electrocardiogram -ECG (adult and pediatric)

Arterial hypertension-hypertensive crisis-hypertension in pregnancy

Coronary artery disease stable and unstable-Cases and Notes

Congestive heart failure diagnosis and treatment and a case of heart failure (video)

The Cardiomyopathies

Pericarditis -pericardial effusion

Constrictive pericarditis: Pathophysiology, diagnosis, echocardiography and treatment

Aortic stenosis -A case of stenosis of the aortic valve

Aortic regurgitation (AR)

Mitral regurgitation. Diagnosis, echocardiography and management. / A clinical case (VIDEO)

Mitral stenosis

Tricuspid regurgitation

Stenosis of the right cardiac valves: Pulmonic stenosis, Tricuspid Stenosis
Infective Endocarditis ( Diagnosis, treatment and a case)

Tachyarrhythmias-supraventricular and ventricular tachycardia

Bradycardia-Bradyarrhythias. Diagnosis,treatment and clinical cases

Pulmonary Hypertension and pulmonary arterial hypertension

A useful link for a free Cardiology journal  (Continuing Cardiology Education, a journal with review articles):

A useful link for drug information : emc

Cardiology free ebook online

Stenosis of the right cardiac valves: Pulmonary stenosis, Tricuspid Stenosis

Stenosis of the right cardiac valves: Pulmonary stenosis, Tricuspid Stenosis

Pulmonic stenosis

Etiology of pulmonic stenosis (narrowing) is usually congenital (in 95 % of cases). An acquired form of pulmonic stenosis can occur with carcinoid heart disease (it can cause both pulmonic stenosis and pulmonic regurgitation). Rheumatic heart disease is a rare cause of pulmonic stenosis and, when present, it is accompanied by multiple valve disease. Large vegetations on a pulmonic valve infected by endocarditis can be a very rare cause of pulmonary stenosis (or regurgitation).
 Children with pulmonic stenosis are most often asymptomatic and the diagnosis is made by auscultation of the systolic murmur at the region of the pulmonary artery by the pediatrician. (See below) Over the years in patients with a significant degree of pulmonic valve stenosis syncopal episodes, angina-like discomfort in physical effort, effort dyspnea or fatigue may occur. 

In neonates with severe narrowing of the pulmonary valve, cyanosis is often observed due to shunting of blood with a direction from right to left through a patent foramen ovale. This shunt is the result of an elevated pressure in the right atrium. The latter is a consequence of increased pressure in the right ventricle, due to the pulmonary stenosis, which imposes an increased load on right ventricular function. Differential diagnosis of cyanosis in the neonate includes, in addition to severe pulmonary stenosis, with a shunt at the level of the atrial septum, some other congenital anomalies such as transposition of the great arteries or pulmonary atresia.

The systolic murmur of pulmonary stenosis is heard louder parasternally at the second left intercostal space. The murmur has a maximum intensity at the middle of systole. The murmur often is preceded by an ejection click heard at the beginning of systole. The click often is better heard lower parasternally, or at the cardiac apex and not at the position of the maximum intensity of the systolic murmur. Usually, the click is not heard in case of a severe stenosis. There is often a wide splitting of the second heart sound, due to the slower ejection of blood by the right ventricle as a result of pulmonary stenosis.

Indications of severity of pulmonic valve stenosis are the following: a murmur with its maximum intensity occurring late in systole, the longer the duration of the murmur, the greater the splitting of the second heart sound and the lower the intensity of the pulmonic component of the second heart sound, which in some cases of severe stenosis of the pulmonary valve may not be audible.

ECG and echocardiographic findings in pulmonic stenosis

ECG: In moderate to severe pulmonic stenosis, a right QRS axis and ECG findings of right ventricular hypertrophy are observed. In severe stenosis, there may also be an indication of right atrial abnormality or dilatation (tall P waves > 2.5 mm in the inferior leads)
Echocardiography in pulmonic stenosis:
It detects the position of the stenosis. In particular, the stenosis (narrowing) can be valvular, subvalvular, or supravalvular (stenosis of the pulmonary artery).
When the stenosis is valvular, in the left parasternal short axis view at the base of the heart, there is thickening, reduced mobility and a dome-shaped opening of the valve leaflets. When a subvalvular stenosis is present, there is a narrowing caused by excess muscle tissue in the right ventricular outflow tract, and when it is supravalvular, a narrowing of the main pulmonary artery or of one of its main branches is observed (a pathologic narrowing of the arterial lumen causing turbulent flow at the site of the stenosis, detected with color flow doppler).

In general, in pulmonic stenosis with the color doppler, turbulent blood flow is observed with aliasing, i.e. an abrupt change in color with a mosaic color pattern in the area of stenosis, due to increased blood flow velocity.

 The severity of the stenosis is determined by examining blood velocity through the stenosis with continuous wave doppler, which provides the maximum pressure gradient. A pressure gradient is the pressure difference that develops between the two sides of a stenotic valve, i.e. the pressure immediately proximal minus the pressure immediately distal to the stenosis. The patient during the examination should be in a relaxed state, in order to avoid an overestimation of the severity of the stenosis.

 Pulmonary artery magnetic resonance imaging (MRI) or helical CT scan can be used to depict a stenosis of the pulmonary artery or its branches.

Treatment of pulmonary valve stenosis

 The decision for treatment  (with transcutaneous balloon valvuloplasty being preferred over surgical treatment) is made when the peak pressure gradient is > 40 mmHg.
Patients with dysplastic valves may not be suitable for balloon valvuloplasty and may require pulmonary valve replacement with a bioprosthetic valve. Percutaneous stented pulmonary valve
implantation is an alternative to surgical replacement of the  pulmonary valve 
 in selected patients with pulmonic stenosis and regurgitation.

A video of valvular pulmonary stenosis (echocardiogram) by Dr Ramachandra Barik
See Link
An echo case: A patient with severe pulmonary stenosis, right ventricular hypertrophy and right to left shunt through a small ventricular septum defect by Dr. Maged Al Ali

Tricuspid valve stenosis (Tricuspid stenosis)

 It is much rarer than mitral stenosis. It is more frequent in women than in men, but overall it is a very rare condition. Tricuspid valve stenosis is usually due to rheumatic fever. Then it does not occur as a single valve disease but it usually coexists with mitral stenosis and it is often accompanied by some degree of tricuspid regurgitation. Among patients with severe mitral stenosis, hemodynamically significant tricuspid stenosis is present in 5-10%.
Tricuspid stenosis of non-rheumatic etiology is even rarer than stenosis due to rheumatic valve disease.
Such rare causes of tricuspid valve stenosis are carcinoid syndrome (which more often causes tricuspid regurgitation), congenital tricuspid atresia, intramyocardial fibrosis and vegetations on the tricuspid valve due to endocarditis (these usually cause valvular regurgitation and rarely valvular stenosis).

Pathophysiology, symptoms and clinical findings in tricuspid valve stenosis

Tricuspid stenosis causes a diastolic pressure gradient (pressure difference) between the right atrium and the right ventricle, resulting in an elevated pressure in the right atrium and in the systemic veins (systemic venous congestion). The pressure gradient depends on the severity of the stenosis and on the blood flow. It increases on inspiration, in which venous return to the large intrathoracic systemic veins increases and therefore the tricuspid transvalvular blood flow increases. The opposite occurs on expiration. A mean diastolic pressure gradient in the tricuspid valve of ≥ 4 mmHg is usually sufficient to result in an increase in mean right atrial pressure to levels that can cause a degree of systemic venous congestion, but this can be reduced by salt intake limitation and the administration of a diuretic.
 Systemic venous congestion causes peripheral edema (swelling at the lower parts of the body, usually the ankles), hepatomegaly (liver enlargement) and ascites (accumulation of fluid in the abdominal cavity). These are the main manifestations of tricuspid stenosis along with fatigue due to the decreased cardiac output.
However, because mitral stenosis usually precedes the development of tricuspid stenosis, many patients have initial symptoms of effort dyspnea and nocturnal dyspnea, as a result of mitral valve stenosis. Typically, when severe tricuspid stenosis develops, dyspnea decreases and is relatively mild compared to the severity of symptoms and signs of systemic venous congestion (edema, ascites, and hepatomegaly).
In tricuspid stenosis, the jugular veins are distended (jugular venous distention on the neck)  and if heart rhythm is sinus ( thus if atrial contraction occurs), very tall a- waves are observed in the jugular pulse. This is the result of an elevated pressure in the right atrium at atrial systole, because the stenotic valve creates an obstacle to blood flow into the right ventricle. Also in the jugular pulse, there is a slow y -descent (negative wave), because emptying of blood from the right atrium to the right ventricle is delayed by the stenotic valve. In severe tricuspid valve stenosis, severe hepatic congestion may result in some cases in the development of cirrhosis of the liver, with jaundice, muscle wasting, large ascites, and splenomegaly.
The diastolic murmur (diastolic rumble) of tricuspid stenosis has some similarities to the diastolic murmur of mitral stenosis. Because mitral valve stenosis usually coexists, the murmur of tricuspid stenosis may not be detected by the examining physician. The diastolic murmur of tricuspid stenosis is usually heard better on the left lower sternal border and on the xiphoid area. Its intensity increases during inspiration. In expiration and during the stress phase of the Valsalva maneuver its intensity decreases (because then the venous blood return to the right atrium and flow through the tricuspid valve decreases).

The ECG and the echocardiogram in tricuspid stenosis 

The ECG in tricuspid stenosis shows right atrial enlargement (increased P wave amplitude in leads II, and V1-see ECG section). In a patient with clinical manifestations of right heart failure, the presence of ECG signs of right atrial enlargement in the absence of ECG signs indicative of right ventricular dilatation or hypertrophy should raise a suspicion of tricuspid valve disease.
The echocardiogram in tricuspid valve stenosis
Echocardiography shows thickening of the leaflets of the tricuspid valve with a dome-shaped valve in diastole (this is similar to the dome-shaped appearance of the mitral valve in diastole observed in mitral stenosis). There is a large dilatation of the right atrium and the superior vena cava (right atrial enlargement is also seen in the postero-anterior chest x-ray).
The area of the functional tricuspid valve orifice can be calculated by using continuous wave doppler in the same way as in mitral stenosis with a calculation of the PHT-pressure half time. A severe narrowing of the tricuspid valve is indicated by PHT ≥190 ms and an orifice area ≤1 cm2. Continuous wave doppler also calculates the mean transvalvular pressure gradient, which according to the European guidelines (by ESC-2012) in severe tricuspid stenosis is ≥ 5 mmHg. In addition, echocardiography indicates whether there is also tricuspid regurgitation, as well as other valvular diseases (often rheumatic mitral disease).
Treatment of tricuspid valve stenosis
Systemic venous congestion is treated by the limitation of salt consumption and administration of a diuretic drug. This treatment of venous congestion may reduce hepatic congestion and improve liver function, thereby reducing the risk of surgery (especially the increased risk of bleeding associated with hepatic dysfunction, since the blood coagulation factors are synthesized in the liver).
In patients with moderate or severe tricuspid stenosis (with a mean transvalvular diastolic pressure gradient o> 4 mmHg and a calculated valve orifice area <1.5-2 cm2), surgical treatment with surgical repair of the tricuspid valve is recommended or, if the repair is not feasible, tricuspid valve replacement with a bioprosthetic valve. Preferably, surgery for tricuspid valve disease is performed along with the operative treatment of commonly coexisting mitral valve disease. Because tricuspid stenosis is very rarely an isolated disorder and is usually accompanied by moderate to severe tricuspid regurgitation and rheumatic mitral valve disease, balloon tricuspid valvuloplasty is very rarely applicable. This is true, since this procedure is contraindicated when there is a significant tricuspid regurgitation, and of course, it does not treat mitral valve disease, which often coexists.

A video (echocardiogram) of Rheumatic tricuspid stenosis and regurgitation
by Dr Venkatesan Sangareddi
A Video Echo of a patient with tricuspid valve stenosis (with tricuspid regurgitation also) and mitral valve stenosis
by Dr. Maged Al Ali

Pulmonic Valvular Stenosis-emedicine/medscape

Holzer RJ, et al. Transcatheter pulmonary valve replacement: state of the art. Catheter Cardiovasc Interv. 2016;87(1):117–128. [PMID: 26423185]  
American College of Cardiology: Tricuspid valve disease: 10 points to remember
Rodés-Cabau J, Taramasso M, O’Gara PT. Diagnosis and Treatment of Tricuspid Valve Disease: Current and Future Perspectives. Lancet 2016;Apr 2

B Phillips. Tricuspid Valve Disease: A Few Points Regarding Right-Sided Heart Failure. The Internet Journal of Thoracic and Cardiovascular Surgery. 2004 Volume 7 Number 1.

Pulmonary Hypertension

Pulmonary Hypertension

It is defined as a mean pulmonary arterial pressure ≥ 25 mmHg measured by right cardiac catheterization.  The normal limits of the mean pulmonary arterial pressure are 11-20 mmHg. A borderline level between 20 and 24 is of unknown clinical significance. These patients should be carefully followed especially when they have conditions predisposing to the development of PH (eg connective tissue disease).
 By echocardiography, an indication of pulmonary hypertension (PH) is a peak velocity of the jet of tricuspid regurgitation > 2.8 m/s (in the absence of pulmonary valve stenosis), or an estimated pulmonary artery systolic pressure  40 mmHg.
Although pulmonary hypertension is often first suspected or discovered by echocardiography, for confirming the diagnosis a right heart catheterization (RHC) demonstrating mean pulmonary arterial pressure ≥ 25 mm Hg is required.
 Another information from the RHC that is central to the diagnosis is the pulmonary arterial occlusion or pulmonary capillary wedge pressure (PCWP).
A hemodynamic classification of pulmonary hypertension (PH) includes
- Precapillary PH, where the pulmonary capillary wedge pressure PCWP is normal ( ≤ 15 mmHg). This applies to PH due to lung disease or chronic thromboembolic lung disease or pulmonary arterial hypertension (PAH) and 
-Postcapillary PH, where the PCWP is elevated (>15 mmHg). This is the case in the most common group of PH, classified under WHO group II ( in this group, PH is due to pulmonary venous hypertension as a result of left heart disease).
PH is a disorder that may develop in multiple clinical conditions and can complicate the majority of cardiovascular and respiratory diseases (especially diseases at a severe stage).

 Classification of severity of pulmonary hypertension.

Mild pulmonary hypertension (PH) is characterized by systolic pulmonary arterial (PA) pressure 35–50 mmHg and mean PA pressure 25–35 mmHg. 
Moderate PH is characterized by systolic PA pressure 50–70 mmHg and mean PA pressure 35–45 mmHg.
Severe PH is characterized by systolic PA pressure >70 mmHg and mean PA pressure >45 mmHg, or pulmonary vascular resistance (PVR) >6-7 Wood units.

In chronic severe PH, although the PA pressure initially is severely elevated, later it may start declining into the moderate to mild range as right ventricular failure progressively worsens. When there is a severe right ventricular failure, the right ventricle cannot generate a high PA pressure. On the other hand, PVR remains severely elevated.

Pathophysiology of pulmonary hypertension

The pulmonary and systemic circulations are in series with each other and normally the total pulmonary and systemic blood flows are virtually identical.
 Despite the same rate of blood flow, the anatomic, hemodynamic, and physiological characteristics of these two sections of the cardiovascular system have substantial differences. The main difference is in vascular resistance: The pulmonary circulation is a low-resistance network of highly distensible vessels.
An elevated pulmonary arterial pressure can be caused by:
An elevated pulmonary arterial resistance (normally pulmonary arterial resistance is about 10 times less than systemic vascular resistance)
An increased blood flow in the pulmonary circulation
An increased pulmonary venous pressure 
Pulmonary hypertension can lead to right ventricular failure. The ability of the right ventricle to adapt to pulmonary hypertension depends not only on the level of pulmonary arterial pressure, but also on the rapidity of the development of PH and on other factors such as the age of the patient, hypoxemia due to a pulmonary disease or concomitant coronary artery disease (these factors can impair the ability of the right ventricle to compensate). The onset of clinical symptoms and signs of right ventricular failure indicates a poor prognosis.

Symptoms of pulmonary hypertension 

The most common symptom is exertional dyspnea, which may progressively worsen. Other manifestations include fatigue (also a very common manifestation), angina (right ventricular hypertrophy and the increased workload of the right ventricle due to the elevated pulmonary arterial pressure can cause right ventricular ischemia), presyncope or syncope, peripheral edema (due to right ventricular failure) and in some cases hemoptysis (in cases of mitral stenosis, or pulmonary thromboembolic disease).

Physical examination in pulmonary hypertension (PH)

An accentuated pulmonic component of the second heart sound (P2) is common. There may be evidence of right ventricular failure with elevated jugular venous pressure (a common finding), a right-sided S3 or S4  and a holosystolic murmur of secondary tricuspid regurgitation, lower extremity edema (this is common), hepatomegaly (enlargement of the liver) and/or ascites. 
Symptoms and signs of the disease that has caused the PH are often present, e.g. paroxysmal nocturnal dyspnea, hypertension, or crackles at the lung bases can be clues to left-sided systolic or diastolic heart failure, a murmur can be a clue to left sided valvular heart disease, rhonchi indicate obstruction of medium sized airways of the bronchial tree, as in chronic obstructive pulmonary disease, clubbing may be seen in some chronic lung diseases, sclerodactyly and telangiectasia can be present in scleroderma, etc.

The ECG in pulmonary hypertension

An electrocardiogram (ECG) may show evidence supportive of PH, but a normal ECG does not exclude the diagnosis. ECG abnormalities can be suggestive of the diagnosis but they are neither specific nor sensitive. ECG abnormalities in cases of moderate to severe PH may include right ventricular strain (inverted T waves in the right precordial leads-this is a relatively sensitive, but not specific sign), P pulmonale, right axis deviation, right ventricular hypertrophy, right bundle branch block, and QTc prolongation. In cases of PH due to a left heart disease, the ECG usually shows evidence consistent with this disease, e.g a P mitrale in mitral valve disease, evidence of a previous myocardial infarction in cases of ischemic cardiomyopathy, left ventricular hypertrophy in hypertensive heart disease or in aortic valve stenosis, etc.

Chest radiography in pulmonary hypertension (PH)

Chest X-ray in pulmonary arterial hypertension (PAH) shows enlarged central pulmonary arteries with rapid tapering of vessels toward the periphery of the lungs (a “pruned tree” appearance) and it may also show enlargement of the right heart chambers.
In other causes of PH, findings depend on the causative disease.
In PH caused by parenchymal lung disease, the chest X-ray may show hyperinflation and bullous disease (suggestive of COPD), or increased interstitial lung markings (suggestive of interstitial lung disease).
In PH caused by left heart disease, the chest X ray may show dilated left heart chambers and signs of pulmonary venous congestion.

Echocardiography in the evaluation of pulmonary hypertension

It can demonstrate enlargement of the right heart chambers (right ventricle and right atrium), signs of right ventricular pressure overload, including paradoxical bulging of the septum into the left ventricle during systole and hypertrophy of the right ventricular free wall.
(Watch this video from 123sonography, which demonstrates these echocardiographic findings Link: 123sonography

Estimation of pulmonary arterial systolic pressure based on the peak velocity of tricuspid regurgitation (TR) by using the continuous wave Doppler signal of TR,  can suggest the presence of pulmonary hypertension. This is a good method to suspect, or suggest PH, but not to accurately measure  PA pressure (Accurate measurement requires right heart catheterization). The peak systolic pressure gradient (pressure difference) between the right ventricle and the right atrium, according to the modified Bernoulli equation is 4V2 , where V= the peak velocity of the TR jet. Thus the peak right ventricular systolic pressure (RVSP) is  4V2+ RAP (where RAP=right atrial pressure). When there is no pulmonary stenosis, RVSP=PASP (PASP: pulmonary artery systolic pressure). Thus, if there is no pulmonary stenosis,  PASP=4V2+ RAP. 
Right atrial pressure (RAP) can be estimated by echocardiography based on the maximum diameter and respiratory variation in the diameter of the inferior vena cava (IVC): 
An IVC diameter < 2.1 cm that collapses > 50% with a sniff suggests a normal RAP of 3 mmHg (range 0–5 mmHg). 
An IVC diameter >2.1 cm that collapses < 50% with a sniff or < 20% on quiet inspiration suggests a high RA pressure of 15 mmHg (range 10–20 mmHg).
 In cases in which the IVC diameter and collapse do not fit this description, an intermediate value of 8 mmHg (range 5–10 mmHg) may be used. Such an approach is more accurate than using for RAP a fixed value of 5 or 10 mmHg. 
However, given the inaccuracies of RAP estimation, it is better to use the continuous wave Doppler measurement of peak TR velocity (and not the estimated PASP) as the main variable for assigning the echocardiographic probability of PH. The echocardiographic probability of pulmonary hypertension (PH) in symptomatic patients with a suspicion of PH can be estimated from the  peak tricuspid regurgitation velocity TRV (expressed in m/s):
 When the peak tricuspid regurgitation velocity, TRV ≤2.8, or is not measurable and other echocardiographic signs suggestive of PH are absent, then the probability of PH is low (for the other suggestive echocardiographic signs of PH see below). 
When TRV ≤2.8, or not measurable and other echocardiographic signs suggestive of PH are present, then the probability of PH is intermediate.
When TRV 2.9–3.4, then the probability of PH is intermediate if other echocardiographic signs suggestive of PH are absent, but the probability is high if other suggestive echocardiographic signs are present.
When TRV >3.4 there is a high probability of PH, regardless of the presence or absence of other echocardiographic signs.
For a good measurement to be obtained the entire Doppler envelope of tricuspid regurgitation (TR) should be visualized with the characteristic bullet-shaped form. Do not measure peak velocity if the jet is not fully formed. Every Doppler velocity measurement should be performed with the Doppler beam as parallel to blood flow as possible. (This rule applies to every Doppler velocity measurement and not only to the measurement of TRV).
Doppler derived right ventricular systolic pressure estimation can be inaccurate in patients with severe tricuspid regurgitation (TR), where TRV may significantly underestimate the pulmonary artery systolic pressure. Thus in patients with severe TR, peak TR velocity should not be used to exclude PH.

Other echocardiographic signs suggestive of pulmonary hypertension (PH) besides TRV

There are several echocardiographic signs suggesting pulmonary hypertension. These signs are used to assess the probability of pulmonary hypertension in addition to tricuspid regurgitation velocity measurement and include: 
An enlarged right ventricle (RV) with RV/ LV basal diameter ratio >1 (LV=left ventricle). 
An enlarged right atrium: Right atrial area (at end-systole) >18 cm2 measured in the apical 4 chamber view.
A dilated pulmonary artery with a diameter >25 mm (measured in the parasternal basal short axis view).
Flattening of the interventricular septum (left ventricular eccentricity index >1.1 in systole and/or diastole). LV eccentricity index is the ratio of the anterior-inferior and septal-posterolateral cavity dimensions at the mid-ventricular level in the parasternal short axis view.
Right ventricular outflow tract(RVOT) acceleration time (AT) <105 msec and/or midsystolic notching of the Doppler signal. AT is the time from the onset to the peak velocity of flow. These two signs are assessed with the pulse wave Doppler immediately proximal to the pulmonary valve in the parasternal basal short axis view.
The RVOT or pulmonary arterial AT (measured with the pulse wave Doppler) can also be used to calculate mean pulmonary arterial (PA) with the following formula
Mean PA pressure = 79 - 0.45(AT)  
  From the same view with continuous wave Doppler interrogation of the flow through the pulmonic valve, an early diastolic pulmonary regurgitation velocity >2.2 m/sec, is also suggestive of PH.
Inferior cava diameter >21 mm with decreased inspiratory collapse (<50 % with a sniff, or <20 % with quiet inspiration).Echocardiography can also show evidence of some etiologies of PH such as left heart disease, or congenital heart disease with a left to right shunt.

General diagnostic workup of patients with suspected PH:

Echocardiography is recommended as a first-line test in case of suspicion of PH.
Lung function test with DLCO (diffusing capacity of the lung for carbon monoxide ) is recommended in the initial evaluation of patients with PH and a high-resolution CT should be considered in all patients with PH, to search for pulmonary disease.
In patients with a working diagnosis of PAH right heart catheterization is needed to measure mean pulmonary arterial pressure, PVR, and PCWP.
When measurement of PCWP is unreliable, left heart catheterization should be considered to measure left ventricular end diastolic pressure (LVEDP). Diagnosis of PAH and specific treatment decisions always require prior diagnostic confirmation with right heart catheterization.
In all patients with PAH routine biochemistry, hematology, immunology, HIV testing and thyroid function tests are recommended to search for a specific associated condition.
Abdominal ultrasound is recommended to screen for portal hypertension.
In patients with unexplained PH a ventilation /perfusion lung scan is recommended to exclude chronic thromboembolic PH (CTEPH). 
 A contrast CT angiography of the pulmonary artery is recommended in the workup of patients with CTEPH.
Patients with CTEPH should undergo screening for thrombophilia, including antiphospholipid antibodies, anticardiolipin antibodies, and lupus anticoagulant.

Note: lung biopsy (open or thoracoscopic)  is not recommended in patients with PAH, according to the recent ESC guidelines.

Clinical classification of pulmonary hypertension (PH) according to the etiology and pathophysiology: 

PH is classified into 5 groups: 


It contains 3 subgroups: 
Pulmonary arterial hypertension (PAH),  
Pulmonary veno-occlusive disease and/or pulmonary capillary haemangiomatosis,  and
 Persistent pulmonary hypertension of the newborn.

Pulmonary arterial hypertension (PAH, group 1)

 It is characterized by the presence of pre-capillary PH ( mean pulmonary arterial pressure  ≥ 25 mmHg and  PCWP is normal ≤ 15 mmHgand pulmonary vascular resistance >3 Wood units, in the absence of other causes of pre-capillary PH such as lung disease or chronic thromboembolic disease or other rare diseases such as pulmonary capillary haemangiomatosis.  Pulmonary arterial hypertension (PAH) includes several different etiologies of PH that share a similar clinical picture and virtually identical pathological changes of the lung microcirculation.  These changes of the lung microcirculation include vasoconstriction, intimal proliferation and fibrosis, medial hyper­trophy and in situ thrombosis. These changes cause a progressive increase in pulmonic vascular resistance (PVR) and thus in right ventricular afterload and right ventricular work.
Etiologically pulmonary arterial hypertension (PAH) is classified as 
Heritable (BMPR2 mutation /Other mutations )
 Induced by drugs and toxins 
PAH associated with: 
Connective tissue disease
 Human immunodeficiency virus (HIV) infection
Portal hypertension 
 Congenital heart disease

PAH is a relatively rare form of pulmonary hypertension. The characteristic symptoms of PAH are dyspnea, chest pain, and syncope and if left untreated, PAH carries a high mortality rate, with the most common cause of death being decompensated right heart failure. There is often a considerable delay in the diagnosis of PAH because the symptoms are insidious and overlap with many common diseases including asthma, chronic obstructive lung disease, and other lung disease and cardiac disease (such as congestive heart failure of many etiologies, or coronary artery disease).
Early diagnosis is important, so that specific treatment for PAH can be initiated because new drugs have been recently developed resulting in a change in the management of this disease, with significant improvement in the quality of life and mortality.The current treatment for PAH can be divided into three main steps: The initial approach includes General measures such as counseling on physical activity and supervised rehabilitation, pregnancy, birth control,  psychosocial support, etc.  PAH patients should avoid pregnancy because it is associated with significant mortality. Immunization of PAH patients against influenza and pneumococcal infection is recommended. Supervised exercise training should be considered in physically deconditioned PAH patients under medical therapy. PAH patients should be encouraged to be active within symptom limits, avoiding excessive physical activity that leads to distressing symptoms.
Supportive therapy such as oral anticoagulants, diuretics, oxygen, digoxin, is important.
Referral to expert centers for PAH treatment and right heart catheterization is indicated in every patient with clinical suspicion of PAH. During right heart catheterization of patients with PAH acute vasoreactivity testing is indicated. 
The second step of PAH treatment includes initial therapy with high-dose with calcium channel blockers only in vasoreactive patients or with drugs approved for PAH in non-vasoreactive patients. These drugs include prostacyclin, an endothelin receptor antagonist, or a phosphodiesterase-5 inhibitor.
Prostacyclin (epoprostenol in continuous intravenous infusion) and prostacyclin analogues ( treprostinil, iloprost) are direct pulmonary vasodilators. 
Endothelin receptor antagonists (e.g., bosentan,
ambrisentan) inhibit the vasoconstricting
effects of endothelin-1.
Phosphodiesterase-5 inhibitors (e.g., sildenafil,
tadalafil) enhance nitric oxide-mediated vasodilation.
The third part of the treatment strategy is related to the response to the initial treatment. In case of an inadequate response,  combinations of the above drugs for PAH, or lung transplantation are considered.

 Pulmonary hypertension due to pulmonary veno-occlusive disease and/or pulmonary capillary haemangiomatosis,

 etiologically is classified as: 
Heritable (EIF2AK4 mutation/other mutations)
Induced by drugs, toxins and radiation, and 
 Associated with: 
Connective tissue disease
HIV infection

Pulmonary veno-occlusive disease and pulmonary capillary haemangiomatosis,

 These are uncommon causes of PH. These two conditions have similarities in pathologic features and clinical characteristics. Another feature, that they have in common is the risk of drug-induced pulmonary edema with PAH. Thus, there is evidence that these two conditions overlap. They also share some important clinical similarities with PAH. 
Pulmonary veno‐occlusive disease is characterized by abnormalities of the pulmonary venules similar to the arteriolar abnormalities seen in idiopathic PAH. and may be idiopathic or associated with scleroderma. Similar to PAH, true pulmonary arterial wedging is difficult during catheterization, but, if successful, the truly wedged PCWP is approximately the same as the left atrial pressure and has normal value. Although the PCWP i.e. the  LA pressure, is normal, the pulmonary capillary pressure is increased due to the obstructive disease of the pulmonary venules. Thus, pulmonary edema can develop.

Group 2 of diseases causing pulmonary hypertension (PH) is PH due to left heart disease 

PH secondary to left heart disease is also called pulmonary venous hypertension or postcapillary PH, because the initial pathophysiologic and etiologic event is the elevated pulmonary venous pressure. This is the most common group of disorders causing PH.
Left heart ventricular or valvular diseases may produce an increase in left atrial pressure. This results in passive backward transmission of pressure to the pulmonary circulation. As a result, the first event is a rise in pulmonary capillary wedge pressure(PCWP) and then also the pulmonary arterial pressure rises. The hemodynamic features are: 
PCWP is elevated (>15 mmHg).
 Diastolic PA pressure is passively increased 
 Pulmonary vascular resistance (PVR) is <3 Wood units. 
The transpulmonary gradient, which is the pressure difference that produces flow in the pulmonary circulation, i.e., mean PA pressure minus PCWP, is <12 mmHg
The transpulmonary gradient is the numerator in pulmonary vascular resistance (PVR) calculation: PVR = transpulmonary gradient/cardiac output.
Causes are classified as :
 Left ventricular systolic dysfunction 
Left ventricular diastolic dysfunction 
Valvular disease, obstruction, and congenital cardiomyopathies 
 Congenital or acquired stenosis of the pulmonary veins 
In PH of the group 2 treatment is of the underlying cause, e.g. treatment for congestive heart failure, or surgery for severe disease of the left heart valves.

Group 3 of the causes of pulmonary hypertension (PH) : Pulmonary hypertension due to lung diseases and/or hypoxia 

These causes of PH are classified as:
 Chronic obstructive pulmonary disease (COPD)
 Interstitial lung disease 
Other pulmonary diseases with mixed restrictive and obstructive pattern 
Sleep-disordered breathing (sleep apnea)
 Alveolar hypoventilation disorders 
Chronic exposure to high altitude 
Developmental lung diseases 
In patients with COPD, mild pH is common, but  moderate PH is only seen in about 5-10% of cases
and severe PH is quite uncommon ( in 2% of cases). respectively. 
Sleep apnea also usually causes mild PH. 
Conversely, severe interstitial lung disease, especially advanced‐stage fibrotic lung disease that obliterates the pulmonary capillaries can cause severe PH.
Severe PH may also be seen with interstitial lung disease due to sarcoidosis and with obesity-hypoventilation syndrome.

In group 3 PH, treatment is of the underlying lung disease or cause. Usually, in case of a lung disease bronchodilators and oxygen are used.

Group 4 of PH:  Chronic thromboembolic pulmonary hypertension and other pulmonary artery obstructions 

This etiologic group includes
Chronic thromboembolic pulmonary hypertension 4 Other pulmonary artery obstructions 
Other intravascular tumors 
Congenital pulmonary arteries stenoses 
Parasites (hydatidosis)
 In thromboembolic PH with proximal thromboembolic disease, the treatment is surgical: pulmonary thromboendarterectomy.

Group 5 of pulmonary hypertension: PH with unclear and/or multifactorial mechanisms

 Hematological disorders: chronic hemolytic anemia, myeloproliferative disorders, splenectomy
 Systemic disorders: sarcoidosis, pulmonary histiocytosis, lymphangioleiomyomatosis, neurofibromatosis 
Metabolic disorders: glycogen storage disease, Gaucher disease, thyroid disorders 
 Others: pulmonary tumoral thrombotic microangiopathy, osing mediastinitis, chronic renal failure (with/without dialysis), segmental pulmonary hypertension
In these patients, there is no specific treatment for PH. Treatment is for the underlying disease. Drugs for PAH are not used in the treatment of group 5 disorders, since there are no randomized trials.

Bibliography and links 

LINK:  2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension 
Galie N, et al. Eur Heart J 2016; 37: 67-119.

Hoeper MM,et al. Treatment of pulmonary hypertension. The  Lancet Respiratory Medicine 2016; 4, 323–336. 


Kiely DG, et al. Pulmonary hypertension: diagnosis and management. BMJ 2013;346:f2028

Infective Endocarditis

Infective Endocarditis

A cardiology case (video): Infective endocarditis of a prosthetic mitral valve -Transesophageal echocardiography 
This is a case of a 32 years old female with a history of mitral valve replacement (with a bileaflet mechanical valve) 3 years before, presenting with fever and a cerebrovascular stroke.
( Echo images are courtesy of dr Abdallah Almaghraby )
To watch the video in full screen click on  the symbol [] at the lower right corner

Infective endocarditis (IE) is a microbial infection of the endocardium or implanted intracardiac materials (eg prosthetic valves, conduits), or pacing electrodes, and indwelling catheters. The most typical pathologic feature of IE is a mobile vegetation associated with valve leaflets. Vegetations are composed of fibrin, platelets, debris, and bacteria. Left-sided lesions are more common than right-sided lesions (the latter are common in intravenous drug
use and congenital abnormalities).
Infective endocarditis (IE) is a serious disease carrying potential for high morbidity and mortality, in part due to the difficulty in establishing an accurate diagnosis early in the course of the disease.
The incidence of IE in the general population is approximately 3-4 cases in 100.000 people per year. 
The most common microorganism involved is staphylococcus aureus , the next most common are streptococci of the oropharyngeal cavity (mostly streptococcus viridians), followed in order of frequency by enterococcus, coagulase-negative staphylococci, other streptococcal species, microorganisms of the HACEK group (Haemophilus, Actinobacillus, Cardiobacterium hominis, Eikenella corrodens, Kingella) group, non HACEK Gram-negative bacteria, and fungi.
Pathogenesis of IE 
In most cases, an injury to the endothelium is involved, being the result of turbulent blood flow at the site of a preexisting cardiac lesion. This results in the deposition of platelets and fibrin on the site and these early deposits are called nonbacterial thrombotic endocarditis. In case of a microorganism present in the blood, for  example due to a dental procedure, or an infection, the microorganism can enter these thrombotic deposits and grow, resulting in the development of vegetations, composed of fibrin, platelets, debris, and bacteria and also often in invasion and destruction of cardiac structures, such as valve tissue, or occasionally invasion of the adjacent myocardium (formation of an abscess).  
 Heart conditions predisposing to endocarditis 
Conditions that predispose to the development of IE by order of frequency include degenerative valve disease , presence of a prosthetic heart valve, intravenous narcotic drug use, rheumatic heart disease and congenital heart disease. 
Conditions predisposing to endocarditis (if significant bacteremia also occurs) are classified according to their relative risk for endocarditis and are the following:
Cardiac conditions with a relatively high or intermediate  risk for IE
Prosthetic valves, including surgically and transcatheter-implanted prostheses, or presence of prosthetic material used for cardiac valve repair (high risk -there is an indication of antibiotic prophylaxis for procedures that can cause bacteremia)
Previous infective endocarditis (obviously high risk)
Indwelling right heart catheters for hyperalimentation are associated with 
high risk for IE, but indwelling right heart catheters for other purposes pose an intermediate risk
 Unrepaired congenital heart disease:
 Coarctation of the aorta, patent ductus arteriosus and arteriovenous fistula are conditions with a high risk for IE. Tetralogy of Fallot has an intermediate risk
Marfan syndrome (relatively high risk)
Valvular heart disease:
 Aortic regurgitation is considered to be associated with a relatively high risk, but calcific aortic stenosis with an intermediate risk. Mitral regurgitation in general is considered to have a relatively high risk, but specifically mitral valve prolapse with regurgitation, as well as mitral stenosis are of intermediate risk for IE. Tricuspid valve disease is also an intermediate risk condition for IE. 
Hypertrophic obstructive cardiomyopathy (intermediate risk)
Nonvalvular intracardiac prosthesis (intermediate risk)
Cardiac conditions with a low risk for IE are:
Mitral valve prolapse without regurgitation
Congenital heart disease with low risk for IE: an uncorrected atrial septal defect and surgically corrected congenital lesions without a prosthesis >6 months after surgery
Cardiac pacemakers
Aortocoronary bypass surgery (negligible risk)

The most important non-cardiac predisposing factors to bacterial endocarditis (by causing bacteremia) are : IV drug use, dental procedures that cause bleeding, oral and upper respiratory tract surgery, genitourinary surgery. 
Antibiotic prophylaxis for IE
Current guidelines have restricted the indications for antibiotic prophylaxis compared to older common practice, because of changes in pathophysiological conceptions and risk-benefit analyses. Cardiac conditions which require prophylactic antibiotic therapy for the avoidance of IE, in case of a procedure predisposing to endocarditis (dental procedures inducing gingival or mucosal bleeding, including professional cleaning, tonsillectomy, adenoidectomy, surgical operations that involve intestinal or respiratory mucosa) are the following :
 Prosthetic heart valves, including bioprosthetic and homograft valves, or a prosthetic material (eg a prosthetic ring) placed for valve repair,
Previous bacterial endocarditis, even in the absence of heart disease  Most congenital cardiac malformations, if not repaired, especially cyanotic lesions (except isolated atrial septum defect which is a low risk condition for IE) or repaired congenital heart disease (CHD) with shunts or conduits, repaired CHD when a residual defect is present , and recent repair of CHD (<6 months) involving prosthetic device or material. 
A cardiac transplant with valve regurgitation due to a structurally abnormal valve
Antibiotic prophylaxis is also recommended before implantation of pacemakers, or implantable defibrillators (ICDs), to avoid infection of the device.
Procedures predisposing to endocarditis are divided into: Procedures with a clear indication for antibiotic prophylaxis (if one of the above cardiac conditions is present) such as dental procedures which induce gingival or mucosal bleeding, (professional cleaning is included), tonsillectomy and  adenoidectomy and
Procedures with a less clear indication for antibiotic prophylaxis, such as operations that involve intestinal or respiratory mucosa. 

Clinical manifestations of IE
The most typical presentation of IE is the presence of fever and a new murmur (in about 85%) of cases. However, fever may be absent in the elderly, uremic, or immunosuppressed. A murmur may be absent with right-sided or mural infection or with infection of an intracardiac device. Nonspecific symptoms such as malaise, fatigue and night sweats are common. Dyspnea is also common.
Congestive heart failure occurs in up to 55% of cases
Neurologic symptoms and findings, are usually indications of an embolic complication and may include clinically apparent cerebral emboli (20%), rupture of a mycotic aneurysm (< 5%), meningitis, or brain abscess (< 5%).
Additional possible manifestations of IE, are due to embolic or immune complex phenomena and  include mucosal petechiae (in about 20% -30% of cases),  Osler’s nodes (painful, tender red nodules on the pads of fingers or toes: 10% -20%), splinter hemorrhages (dark red linear streaks under the nails in about  10% -20%), an arterial embolism (the clinical picture depends on the site of embolism,see below),  Janeway lesions (these are more rare, they are red, macular, nontender lesions on the fingers, palms, or soles, observed in  < 5% of IE cases), splenomegaly (in about 30% of cases), and Roth’s spots (retinal hemorrhages: < 5%). These classic physical findings are not sensitive and (also not specific) for the diagnosis of IE.
Systemic embolization occurs in about 20% - 40% of cases of IE and may result in manifestations of  an acute stroke (cerebral emboli), or it can mimic peritonitis (embolization to the spleen, kidney, or bowel), a pulmonary embolism (from IE involving the right side of the heart), an acute coronary syndrome (coronary artery emboli), or it may result in a cold extremity with reduced or absent pulse (embolization of a peripheral artery).
In summary, the clinical picture of IE is highly variable, ranging from subtle and slowly progressive symptoms to acute severe congestive heart failure due to severe valvular regurgitation. IE can be divided into acute and subacute.
Acute infective endocarditis, the most common cause of which is staphylococcus aureus, is associated with rapid symptom onset, often with high fever and it is a more invasive infection which tends to produce large vegetations (2 mm to 2 cm), rapid valve destruction and, commonly, embolic complications. Invasion of myocardium with the formation of an abscess cavity, is also common.
With subacute infective endocarditis, streptococcus viridans (a microorganism of the oral cavity) is the most common causative agent. Clinical course is characterized by slow onset with vague or nospecific symptoms, such as low-grade fever, malaise, fatigue, weight loss, flulike symptoms, chills, night sweats, and musculoskeletal aches.  It  leads to valve lesions and valve dysfunction but with a more gradual course, in comparison to acute IE. It tends to produce smaller vegetations than those observed in acute IE. 
Diagnosis of IE
 The modified Duke criteria are widely used for the diagnosis of IE. A combination of 2 major criteria, or the combination of 1 major and 3 minor criteria, or five minor criteria will constitute a definite clinical diagnosis. 
The major diagnostic criteria can be summarized as 
 Positive blood cultures and 
An abnormal echocardiogram with typical findings for IE. 
A more detailed description of the major clinical diagnostic criteria is the following:
• A positive blood culture for infective endocarditis, as defined by the recovery of a typical microorganism from two separate blood cultures in the absence of a primary focus.
(Typical microorganisms include viridans streptococci, community-acquired staphylococcus aureus or enterococcus species, streptococcus bovis, HACEK group, abiotrophia species and granulicatella species), or
• A persistently positive blood culture, for a microorganism consistent with IE from either blood samples obtained more than 12 hours apart, or all three, or a majority of four or more separate blood samples, with the first and last obtained at least 1 hour apart, or
• A positive serological test for Q fever, with an immunofluorescence assay showing phase 1 IgG antibodies at a titre >1 : 800, or
• Echocardiographic evidence of endocardial involvement:
-An oscillating intracardiac mass on a cardiac valve or its supporting structures, in the path of regurgitant jets, or on implanted material in  the absence of an alternative anatomical explanation, or
-An abscess, or
-New partial dehiscence of a prosthetic valve, or
-New valvular regurgitation.

The minor criteria are: 
Predisposing cardiac lesion
IV drug use
Vascular phenomena (arterial embolic, septic pulmonary infarcts, Janeway lesions),
Immunologic phenomena (such as Osler nodes, Roth spots, glomerulonephritis, or a positive rheumatoid factor)
Microbiologic evidence (positive blood cultures not meeting major criteria or evidence of active infection with an organism consistent with infective endocarditis)

I recommend the following videos, because appart from a summary of the topic, they also provide images of some physical signs of IE, such as mucosal petechiae, Osler’s nodes, splinter hemorrhages, Janeway's lesions, Roth spots. LINKS :

Diagnostic tests
In IE, bacteremia is almost constant, therefore positive blood cultures remain the cornerstone of diagnosis and permit identification of the causative micro-organism and susceptibility testing. Samples for blood culture should be taken before antibiotic administration (At least three sets of blood cultures at 30-minute intervals, each containing 10 ml of blood, incubated in both aerobic and anaerobic culture media). The sample should be obtained from a peripheral vein rather than from a central venous catheter with a meticulous sterile technique. This almost always is sufficient to identify the usual causative microorganisms. 
Blood culture-negative IE refers to IE in which no causative microorganism can be grown and identified by the usual blood culture methods and it can occur in approximately 10- 20% of all cases of IE.  It often poses important diagnostic and therapeutic dilemmas. Blood culture-negative IE commonly arises as a consequence of previous antibiotic administration, or it is IE caused by fungi or fastidious bacteria (especially obligatory intracellular bacteria). Such microorganisms need culture on specialized media, in order to be isolated. Moreover, their growth is relatively slow.

Four echocardiographic findings are major criteria for the diagnosis of IE: a vegetation,  an abscess or pseudoaneurysm , a new dehiscence of a prosthetic valve and a new valvular regugitation. With current technology the sensitivity for the diagnosis of vegetations for  transthoracic echocardiography (TTE) in native and prosthetic valves is 70% and 50%, respectively,  and for transesophageal echocardiography (TEE)  95% and 92%, respectively (roughly let us say more than 90 %).  Specificity is approximately 90% for both TTE and TEE.
Some echocardiographic findings, that can be observed in infective enocarditis (IE):
A vegetation, on echocardiography, appears as an irregularly shaped, discrete echogenic mass which is adherent to, but distinct from, the endocardial surface or an intracardiac device. Oscillation of the mass is supportive for the diagnosis, but not mandatory.
An abscess, on echocardiography, is a thickened, nonhomogeneous area near a valve with echodense or echolucent appearance. Evidence of flow into the region is supportive for the diagnosis, but not mandatory.
Perforation of a valve leaflet is defined as interruption of tissue continuity of valve leaflet with demonstration of flow with color flow doppler, through the defect.
Dehiscence of a prosthetic valve is shown by demonstration of paravalvular regurgitation by transthoracic or transesophageal echocardiography, with or without a rocking motion of the prosthesis.
Pseudoaneurysm is a perivalvular cavity communicating with the cardiovascular lumen and in echocardiography it appears as a pulsatile perivalvular echo-free space (an echolucent cavity) with color-Doppler detected entering this space.
A valve aneurysm is a saccular outpouching or bulging of valvular tissue (meaning that  a portion of the valvular tissue protrudes outward).

Treatment of IE  
According to the latest guidelines, the best management of IE can be achieved  via an "endocarditis team", a multidisciplinary collaboration among cardiologists, cardiac surgeons, and infectious 
disease specialists (Although, this is not always quite possible).
In IE, prompt initiation of parenteral antibiotic therapy is important, because the rate of complications, such as embolization, decreases rapidly within several days, after initiation of proper antibiotic treatment. 
In severely ill patients with IE initial empirical antibiotic treatment (before pathogen identification) should start immediately after obtaining three separate blood cultures at 30 minute time intervals. When the pathogen is identified the antibiotic regimen can change according to the specific microorganism and its antibiotic subsceptibility. Generally in IE the duration of antibiotic treatment is usually about 4-6 weeks. Repeat sets of blood cultures
after the initiation of antibiotic treatment are obtained every  48 hours, until the resolution of bacteremia is confirmed.
Indications for surgery in IE include: 
Heart failure with pulmonary edema or cardiogenic shock, or signs and symptoms of heart failure, or valve dysfunction with echocardiographic signs of poor haemodynamic tolerance.
Findings suggesting that the infection cannot be controlled or is allready uncontrolled such as persisting positive blood cultures despite appropriate antibiotic therapy and adequate control of septic metastatic foci,  or
 local findings of uncontrolled infection such as abscess, false aneurysm, fistula, or an enlarging vegetation,
or IE by fungi or multiresistant organisms, or
 prosthetic valve endocarditis caused by staphylococci or non-HACEK gram-negative bacteria (this is a class IIa indication, meaning that surgery probably should be considered but not as an absolute indication).
Surgery is also indicated in infective endocarditis for prevention of embolic complications:
After an embolic episode in a patient with IE involving a native or prosthetic aortic or mitral valve with persistent vegetations >10 mm despite appropriate antibiotic therapy.
IE involving an aortic or mitral valve (native or prosthetic) with very large vegetations >30 mm (this is a relative-class IIa-indication for surgery).

The objective of surgery is the total removal of infected tissues and repair of cardiac damage, including repair of the affected valve, or replacement of the affected valve with a prosthetic one.
 Proposed antibiotic regimens for empirical treatment (before pathogen identification)  are the following: 
For community-acquired endocarditis of native valves, or late endocarditis of prosthetic valves (≥12 months post surgery) : Ampicillin 12 g/day i.v. in 4–6 doses+ (Flu)cloxacillin or oxacillin + Gentamycin (for drug dosages see below) or
 for patients allergic to penicillin, a very good regimen is Vancomycin + Gentamycin (for dosages see below)
For early prosthetic valve endocarditis (<12 months post surgery) or for healthcare associated endocarditis 
Vancomycin +Gentamycin +Rifampin (rifampin is recommended only for prosthetic valve IE and should be started 3–5 days later than the other two drugs). For drug dosages see below.

Therapy of I E caused by some common specific microorganisms
Treatment for Streptococus viridans: (and also in general for oral and digestive streptococci) : Penicillin G 12–18 million U/day i.v. either in 4–6 doses or continuously or 
Amoxicilline 100–200 mg/kg/day i.v. in 4–6 doses
or Ceftriaxone 2 g/day i.v. or i.m. in one dose.
Treatment duration is 4 weeks.
Alternative treatment for 2 weeks : one of the above anibiotics + 
an aminoglycoside ( Gentamycin 3 mg/kg/day i.v. or i.m. in one dose, or Netilmycin 4–5 mg/kg/day i.v. in one dose).
For patients allergic to beta-lactam antibiotics (penicillines, cephalosporines) : Use for 4 weeks Vancomycin 30 mg/kg/day i.v. in 2 doses.
For strains relatively resistant to penicillin (MIC 0.250–2mg/l) : Penicillin G 24 million U/day i.v. either in 4–6 doses or continuously or Amoxicilline 200 mg/kg/day i.v. in 4–6 doses, or Ceftriaxone for 4 weeks + 
Gentamycin for 2 weeks (the last two antibiotics with dosages as above).
or in allergic patients Vancomycin (4 weeks) + Gentamycin (2 weeks), dosages as above

Methicillin-sensitive staphylococcus (native valve infection) treatment duration is for 4-6 weeks : (Flu)cloxacillin or oxacillin 12 g/day i.v. in 4–6 doses
 If the patient is allergic to penicillin, or for methicillin-resistant staphylococci (native valves) treatment is for 4-6 weeks with: Vancomycin 30–60 mg/kg/day i.v. in 2–3 doses/ or Daptomycin 10 mg/kg/day i.v. once daily.
For staphylococcus (Methicillin-susceptible) endocarditis of  prosthetic valves  (Flu)cloxacillin or Oxacillin (for ≥ 6 weeks) + Rifampine (for ≥ 6 weeks) 900–1200 mg i.v. or orally in 2 - 3 divided doses   Gentamycin (for 2 weeks).
For staphylococcus (Methicillin-resistant) endocarditis of  prosthetic valves, or allergy to penicillin, instead of Flucloxacillin, or Oxacillin use Vancomycin, with the same other 2 drugs. Treatment duration is the same.

Enterococcus:   4-6 weeks treatment with Amoxicillin 200 mg/kg/day i.v. in 4–6 doses  +  Gentamycin for 2-6 weeks
Alternative treatment (in penicillin-allergic patient or resistant strain of enterococcus):Vancomycin + Gentamycin, both for 6 weeks (Dosages as usual, see above). 

(Pediatric doses of antibiotics in IE: Penicillin G 200,000 U/kg/day i.v. in 4–6 divided doses, Amoxicillin 300 mg/kg/day i.v. in 4–6 divided doses ,
Ceftriaxone 100 mg/kg/day i.v. or i.m. in one dose,
Gentamycin 3 mg/kg/day i.v. or i.m. in 1 dose or 3 equally divided doses,

 Vancomycin 40 mg/kg/day i.v. in 2 or 3 equally divided doses,
Rifampin 20 mg/kg/day i.v. or orally in 3 equally divided doses 

Treatment for HACEK group microorganisms. These are slow growing fastidious gram negative bacilli. They are susceptible to ceftriaxone, other third-generation cephalosporins and quinolones. Standard treatment is ceftriaxone 2 g/day ( treatment duration in native valve enodcardis is 4 weeks and in prosthetic valve endocarditis is 6 weeks.

For Gram-negative bacteria that do not belong to the HACEK group the recommended treatment is early surgery plus long-term (at least 6 weeks) therapy with bactericidal combinations of beta-lactams and aminoglycosides. A quinolone or cotrimoxazole may be added to the above treatment.

Cardiac device related endocarditis (CDRIE) is a special and difficult problem (microbial infection of the leads of a pacemaker, or implanted defibrillator). Cardiac device (pacemaker, or implanted defibrillator) infection is generally classified in two categories: pocket infection and endocarditis. Patients may present with regional or systemic manifestations, which can include : 
In cases of pocket infection : erythema (redness), pain, local warmth, purulent discharge, or erosion of the skin.
In cases of endocarditis: fever is the most common symptom, fatigue, malaise, loss of appetite are common, and local signs of pocket infection may be present. A septic pulmonary embolus may occur.
with PM/ICD infections may present with regional or
systemic symptoms. Erythema, pain, erosion, redness,
increased warmth, purulent drainage, and cellulitis are fre-
quent regional findings in pocket infections.In endocarditis,
fever and rash are present in addition to regional findings.
Positive surface and blood cultures suggest the presence of
a device infection.
Three or more sets of blood cultures are recommended before prompt initiation of antimicrobial therapy and a transesophageal echocardiogram (TEE) must be performed in patients with suspected CDRIE with positive or negative blood cultures, to assess for the presence of lead-related endocarditis and heart valve infection. TEE may show electrode or valvular vegetations.
 In the majority of patients, CDRIE must be treated by complete hardware (device and leads) removal and prolonged antibiotic therapy (i.e. before and after hardware removal). The same treatment is also recommended in presumably isolated pacemaker or defibrillator pocket infection (i.e infection at the site, where the battery of the device has been implanted).Before reimplantation of the device a re-evaluation of the indication for implantation is necessary, because in some cases, reimplantation is not necessary. The new device should be implanted on the contralateral side. Immediate reimplantation should be avoided, because there is a significant risk of new infection. Blood cultures should be negative for at least 72 hours before placement of a new device. The decision on the timing of reimplantation needs a consideration of several factors such as persistent bacteremia, persistent vegetation and how dependent is the patient from the pacemaker or the implantable cardioverter defibrillator. When there is evidence of remnant valvular infection, implantation should be delayed for at least 14 days. Temporary pacing should be avoided if possible, because it is a risk factor for subsequent cardiac device infection. In a pacing-dependent patient, temporary use of active fixation leads connected to an external device can be a "bridging strategy", until the placement of a new permanent device is considered safe.

Bibliography and Links :

I recommend this video (by 123sonography) showing echocardiography in native valve endocarditis  Link:
Echo in Endocarditis-Prof. Thomas Binder

2015 ESC Guidelines for the management of infective endocarditis

Hoen B, Duval X. Infective endocarditis. N Engl J Med 2013; 368:1425–1433

Baddour LM, Wilson WR, et al: Infective endocarditis: diagnosis, antimicrobial therapy and management of complications. Circulation 2005;111: e394–e434

Li JS, Sexton DJ, et al: Proposed modifications to the Duke criteria for the  diagnosis of infective endocarditis, Clin Infect Dis 2000;30:633–638