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

Prosthetic heart valves

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

These are sites that contain easy-to-use medical calculators, to calculate for example body surface area (BSA), body mass index (BMI), estimated glomerular filtration rate (eGFR), CHA₂DS₂-VASc Score for Atrial Fibrillation Stroke Risk, 
 10 -year cardiovascular risk scores,TIMI and GRACE risk scores for acute coronary syndromes, Duke criteria for infective endocarditis, Cardiac index and systemic vascular resistance calculators, Calorie calculators/ Drug dosage calculators, etc


Online Medical Calculators-Medicine World org

Medscape-Medical Calculators for medical professionals

LINKS TO OTHER FREE SOURCES OF MEDICAL INFORMATION  (About Cardiology, emergency medicine, internal medicine, and other clinical fields)

Cardiology cases-videos by Dr Chatziathanasiou  
(This is my own channel ! It contains cardiology cases. It is under development -more videos are being continuously added).

Clinical Advisor - Decision Support in Medicine

The Merck Manual - MSD Manual Professional Edition-Cardiovascular Disease

Radcliffe Cardiology - Information for Cardiology Professionals

NICE Evidence search: Cardiology

Continuing Cardiology Education, a journal with review articles):


E medicine-Medscape-Cardiology

The Echo-Journal-Echocardiography videos and Tutorials

123 sonography you tube channel (by Professor of Cardiology and echocardiography Thomas Binder) Link

ECG Library-Life in the fast lane medical blog

Dr. Smith's ECG blog

Cardioserv blog-Echocardiography

CCC Live Cases (Interventional cardiology cases and videos)

Cardiology News  (site for physicians about cardiology news and new developments in cardiovascular medicine)

European cardiology review (ECR)  This is a free journal, but to view all contents you need to register online to the webpage (Registration is free -Takes about 5 minutes)

Prof N Kumar Cardiology lectures (videos about interventional cardiology -electrophysiology-ECG etc)

DeBakey Institute For Cardiovascular Education and Training-videos-cardiology lectures

UofL Internal Medicine Lecture Series-cardiology lectures (videos)

Dr. John M ( a medical-cardiology blog)


NEJM blog-cardiology posts


FREE BOOKS DOWNLOAD (freebookcentre net)


Cardiology free ebook online

Prosthetic heart valves ( a consise overview)

Prosthetic heart valves

There are two main types of prosthetic heart valves, mechanical valves which are durable but require chronic anticoagulation
because of thrombogenicity and biological valves which are less durable, but also less thrombogenic. Biological valves do not require anticoagulation (unless there are other reasons for anticoagulation, such as atrial fibrillation).

The hemodynamic characteristics of a prosthetic heart valve (flow velocity, peak pressure gradient, mean pressure gradient) are influenced by the type of the valve and the diameter of the valve ring (smaller diameter entails a higher peak flow velocity and pressure gradient). An echocardiogram should be performed after the implantation of a prosthetic valve so that the findings can be used for future comparison.

Mechanical heart valves

Mechanical heart valves consist of a sewing ring and the occluder (the moving part of the valve which moves from the opening to the closing position at the appropriate phases of the cardiac cycle). Bileaflet mechanical valves, the type of mechanical valves currently used, have two occluders (leaflets), while single tilting disk and cage-ball valves have one occluder ( a disk, or a ball) respectively.
Tilting disk valves: They are classified in single and double tilting disk (bileaflet) valves. Nowadays mainly double disk (bileaflet) valves are used.

Single tilting disk valves (Medtronic-Hall, Omniscience, Bjork-Shiley, 
Lillehei-Kaster) consist of a ring and a disk, that shifts between the opening position and the closing position, supported by metal struts. In the opening position the disc forms with the plane of the ring an angle of 60-80 degrees.

For a single tilting disk mechanical valve at the aortic position, the peak blood velocity is usually in the range of 1.6-3.3 m /sec. At the mitral position, the peak velocity is usually 1.4-1.7 m /sec.

The bileaflet (double disk) valves (e.g. St Jude Medical, Carbomedics, Sorin Bicarbon, Medtronic Open Pivot, ATS valve, On-X) consist of two semi-circular pyrolytic carbon disks attached to the ring of the valve with special hinges. At the opening position, each disc forms an angle of 75-90 degrees. (This is a general description, but there are some differences in certain technical details between valve types).

The bileaflet valves are the mechanical valves currently used because they have better hemodynamic characteristics ( lower transvalvular gradients) and low thrombogenicity in comparison to other types of mechanical cardiac valves, such as cage ball or tilting single disk valves

 For a double disk mechanical valve in the aortic position the peak blood velocity is usually 2-3 m /sec (up to 3.3 m /sec for valves with a smaller diameter) and the peak pressure gradient 16-45 mm Hg.(Higher values apply to a small diameter valve ring: 19 or 21 mm). Of course, these limits are approximate and not absolute.

For a double-disk mechanical valve at the mitral position, the mean pressure gradient is usually 2.5-7 mm Hg and the peak velocity is 1.1-2 m /sec.

Small deviations may be observed from the above flow velocity measurements and pressure gradients. An echocardiogram should be performed after the implantation of a prosthetic valve so that the measurements can be used for future comparison

The Cage-Ball Valve (Starr-Edwards) is an old valve type, which has been in use for twenty-five years, but nowadays it is not selected for implantation. It consists of a ball of silicone, swinging in a cage of metal alloy (cobalt-chromium). On the valve base, there is a sewing ring that serves to secure the valve to its position. When the valve opens, the ball moves away from the ring and blood flows around it, while on closing the ball fits onto the ring, preventing blood regurgitation. This valve is bulky (unsuitable for patients with a small aortic annulus or small left ventricle). Turbulent flow also occurs around the sphere. Due to the above, a higher pressure gradient is generated compared to other valves. In addition, turbulent flow causes endothelial injury, so this valve is more thrombogenic.  On auscultation of the patient, multiple opening sounds are heard due to the impact of the ball on the cage supports. There is also a metallic closing sound.

Bioprosthetic heart valves (Biological tissue valves or bioprostheses) 

Bioprosthetic valves (bioprostheses) can be heterografts or xenografts (valves made of animal tissue), which are composed of
porcine, bovine, or equine tissue (valvular or pericardial), or homografts, which are preserved human aortic valves. In cardiac auscultation, normally functioning bioprosthetic (biological) valves do not differ from normal native valves. There are several types of bioprosthetic valves: .
Heterografts or XenograftsHeterografts include stented and stentless biological valves. In stented valves, the biological valve tissue is mounted on a rigid stent (plastic or metallic), also called sewing ring, covered with fabric. Conversely, stentless bioprostheses do not include a stent, thus they use the patient’s native aortic root as the valve stent. 
 Heterografts are: 1) Porcine valves properly suited to a suture ring made of synthetic material. Such valves are: Carpentier-Edwards, Hancock II and Mosaic (Medtronic). With echocardiography, for the Carpentier-Edwards valve at the mitral position, the expected peak velocity is about 1.5-2 m /sec and the expected mean pressure gradient of 5-9 mmHg. In the aortic position, the expected peak velocity is 2-3 m /sec and the expected mean pressure gradient  8-20 mmHg.

A more recent development is the introduction of stentless porcine valves. The absence of a stent enables implantation of a larger valve for a given native annulus size, resulting in a larger effective orifice area (EOA) and a lower transvalvular pressure gradient, which is an advantage of these valves. Such are: Edwards Prima Plus, Medtronic Freestyle, and Toronto SPV (St. Jude Medical.)

 2) Valves made of bovine pericardium. These include the following: Perimount series valves (Edwards LifeSciences). and Ionescu-Shiley, which is no longer produced.
Pericardial valves are also two valve types used in transcatheter aortic valve implantation (TAVI): SAPIEN XT (Edwards LifeSciences) made of bovine pericardium and CoreValve (Medtronic) made of porcine pericardium. The valves used for TAVI are trileaflet bioprosthetic valves mounted in a wire mesh stent. Delivery of the valve is performed over a catheter and the stent is expanded in the position of the aortic valve. TAVI can be performed with a catheter advanced from the femoral artery in retrograde fashion across the aortic valve, or from a small thoracotomy with the catheter passed through the apex of the left ventricle and advanced across the aortic valve. This procedure is used for calcific aortic stenosis with the native valve being compressed but remaining in place. TAVI is indicated in patients with severe symptomatic aortic stenosis who have a high risk of adverse surgical outcomes due to comorbidities. Possible complications include stroke, vascular complications (at the entrance site at the femoral artery), and paravalvular regurgitation

Homografts or allografts
Preserved aortic valves from human cadavers.
Usually taken 24 hours after the donor's death, they are sterilized by antibiotics and maintained at a temperature of -196 ° C. The recorded Doppler velocities are approximately the same as those of native aortic valves.
Autograft  (Ross operation)
Pulmonary autograft is the patient's own pulmonary valve implanted to replace a pathologic aortic valve, during a Ross operation. The pulmonary autograft consists of the pulmonary valve with its ring and a small part of the main pulmonary artery. The aortic valve and the aortic root are replaced with the autograft, to which the coronary arteries are then implanted. Subsequently, a pulmonary allograft (cadaveric graft) is implanted in place of the pulmonary valve. Advantages of this operation are that the autograft placed in the aortic position has a very good hemodynamic behavior and better durability than other biological valves. The disadvantage is that it is a technically difficult procedure that requires a long duration of extracorporeal circulation and is only performed in a few cardio-surgical centers with experience.

Selection of the type of prosthetic heart valve

The patient should be informed about the advantages and disadvantages of each option. Mechanical valves have greater durability, but need lifelong anticoagulation, whereas bioprostheses are less durable, but have the advantage of a lower thrombogenic potential and do not need lifelong anticoagulation.
In favor of a mechanical prosthetic valve are the following:
Age< 65 with a long life expectancy, no contraindications for anticoagulation, or a patient already receiving anticoagulation treatment.
In favor of a biological prosthetic valve are the following:
Age  65, or a limited life expectancy,  a contraindication for anticoagulation, or a woman of child bearing age who desires pregnancy.

Antithrombotic treatment in patients with prosthetic heart valves

Bioprosthetic valves:

Bioprosthetic (biological) valves are clearly less thrombogenic than mechanical ones, so they do not necessarily need anticoagulation. However, there is a risk of embolism during the initial postoperative period (mechanism: thrombus production on the prosthetic valve support ring). According to the guidelines in patients with a bioprosthetic valve in the mitral or tricuspid position, it is a good practice (with a category IIa-not absolute- indication) to administer anticoagulation with a vitamin K antagonist (acenocoumarol or warfarin) for the first 3 months after valve implantation. Postoperatively heparin (unfractionated or low molecular weight) is initially administered and treatment with a vitamin K antagonist (VKA) is also initiated. When the INR reaches therapeutic levels (2-3) heparin is discontinued and oral anticoagulant treatment is continued (with INR 2-3) for 3 months After 3 months, the risk of thromboembolism is much lower. (INR = international normalized ratio). Therefore, anticoagulation with VKA is discontinued, and permanent antithrombotic treatment with aspirin 80-100 mg (or clopidogrel 75 mg) per day is initiated.
Oral anticoagulation using a VKA should also be considered for the first 3 months after surgical mitral or tricuspid valve repair (a class IIa indication)
 After surgical implantation of a bioprosthetic valve at the aortic position, because at this position there are higher blood flow velocities resulting in less risk of thrombosis, guidelines recommend administering only low dose aspirin  (eg 80-100 mg daily) for the first 3 months after surgery. This has a Class IIa indication.
However, guidelines allow the option to give these patients (with an aortic bioprosthesis) in the first 3 months a VKA instead of aspirin but with a  class IIb indication ( a "weak" indication).
Exception: In patients with a bioprosthetic valve that also have other risk factors for thromboembolism (such as: a previous embolic episode, atrial fibrillation, or severe left ventricular systolic dysfunction with an ejection fraction  35% or a hypercoagulable state), anticoagulation with  INR 2-3 is administered lifelong (and not just for the first 3 months). This is an absolute (class I) indication for permanent anticoagulation.
After transcatheter aortic valve implantation (TAVI), dual antiplatelet therapy is administered for the first 3-6 months. This is followed by lifelong single antiplatelet therapy in patients who do not need oral anticoagulation for other reasons. In case of TAVI, where an additional thromboembolic risk factor (atrial fibrillation, left ventricular systolic dysfunction, hypercoagulability) is also present, a vitamin K antagonist (VKA) is permanently administered with target INR 2-3, while aspirin 80-100 mg, or clopidogrel 75 mg daily is given during the first year and then it is discontinued

Mechanical prosthetic heart valves

Lifelong oral anticoagulation with a vitamin K antagonist (VKA) is recommended for all patients with mechanical prosthetic valves (this is an absolute-class I-recommendation). Note that the new oral anticoagulants (NOACs) are not used in patients with mechanical cardiac valves. The target INR depends on the thrombogenicity of the type of the mechanical valve prosthesis and patient risk factors (such as mitral or tricuspid valve replacement, previous thromboembolism, atrial fibrillation, mitral stenosis of any degree, severe left ventricular systolic dysfunction with EF <35%).
Thrombosis and thromboembolism risks are greater with a mechanical valve in the mitral than in the aortic position.

If the patient has a mechanical valve prosthesis of low thrombogenicity and no other risk factors for thromboembolism the target INR is around 2.5, but if 1 or more of the other risk factors are present, then the target INR is around 3.

Mechanical heart valves with a low thrombogenicity are most bileaflet valves: St Jude Medical, Carbomedics, Sorin Bicarbon, Medtronic Open-Pivot, ATS, On-X (all these are mechanical bileaflet valves), and also Medtronic Hall (a single disk valve).

If the patient has a mechanical valve prosthesis of medium thrombogenicity and no other risk factors for thromboembolism the target INR is around 3, but in the presence of 1 or more of the other risk factors the target INR is around 3.5
Mechanical valves of medium thrombogenicity are some other bileaflet valves with insufficient data.

If the patient has a mechanical valve prosthesis of high thrombogenicity and no other risk factors for thromboembolism the target INR is around 3.5, but in the presence of 1 or more of the other risk factors, the target INR is around 4.
Mechanical valves of high thrombogenicity are: the ball-cage valve (Starr-Edwards) and most single disk valves (with the exception of Medtronic Hall) such as Lillehei-Kaster, Omniscience, Bjork-Shiley and other single tilting-disc valves.
Good management of anticoagulation is important since a high variability of the INR is a strong independent predictor of
reduced survival after heart valve replacement with a mechanical prosthesis.

The addition of low-dose aspirin (75-100mg/day) to VKA should be considered if thromboembolism occurs, despite an adequate INR (IIa C)

 In cases when VKA treatment should be interrupted, bridging with therapeutic doses of unfractionated heparin (UFH) or low molecular weight heparin (LMWH) is recommended.

Patients with mechanical heart valves undergoing a percutaneous coronary intervention (PCI) 

In patients with mechanical heart valves undergoing a percutaneous coronary intervention (PCI) with stenting, there is a need for a temporary combination of anticoagulant (VKA) and antiplatelet drugs( aspirin, clopidogrel), a situation that increases the risk of bleeding. Guideline recommendations for these patients can be summarized as follows:
Initially triple antithrombotic treatment (VKA+aspirin+clopidogrel) is administered for 1 month (it may be given for up to a maximum duration of  6 months if the patient is considered to have a high thrombotic risk and a low bleeding risk). After the period of triple antithrombotic treatment, dual therapy (VKA+clopidogrel, or VKA+aspirin) follows until up to 12 months after coronary stent implantation. Then antiplatelet treatment is discontinued and the patient continues only VKA (anticoagulation). 
In patients with a high bleeding risk (when bleeding risk is considered as more important than ischemic risk), triple antithrombotic treatment is not given. Then treatment after PCI includes only a period of dual antithrombotic therapy (VKA+ clopidogrel) which can last up to 12 months. After that antithrombotic therapy continues only with the VKA. A high ischemic risk ( a high risk for a subsequent myocardial infarction) is considered to be present in patients presenting with an acute coronary syndrome or having certain characteristics of the coronary lesion (e.g. presence of thrombus, a complex lesion), whereas the bleeding risk is estimated by using the HAS-BLED score.
HAS-BLED stands for:
Hypertension (systolic >160 mmHg) or
Abnormal renal function (creatinine >2.2 or dialysis or renal transplant)

Abnormal liver function (Cirrhosis or Bilirubin >2x Normal or AST/ALT/ALP >3x Normal)
Stroke (history of previous stroke)
Bleeding (
Prior major bleeding or predisposition to bleeding
Labile INR (unstable or high, remains in the therapeutic range for < 60% of the time)
Elderly (> 65 years)
Drugs (medication usage that predisposes to bleeding, such as NSAIDs or antiplatelet drugs)  or

 alcohol(≥ 8 drinks/week)
The presence of each of the above adds 1 point to the score.
A HAS-BLED score of ≥3 indicates high risk for major bleeding ( defined as intracranial hemorrhage, or bleeding requiring hospitalization, or hemoglobin decrease > 2 g/dL, and/or transfusion) 

Clinical and echocardiographic follow-up of a patient with a prosthetic heart valve

In general, emphasis should be placed on informing the patient about proper adherence to anticoagulation and endocarditis prophylaxis.
According to the guidelines of the European Society of Cardiology (ESC) a patient who undergoes a valve replacement requires after 6-12 weeks a complete follow-up examination, including clinical examination (history of possible symptoms, cardiac auscultation to check for the expected auscultatory findings for the type of prosthetic valve and also to check for a possible new cardiac murmur), ECG, chest X-ray, transthoracic echocardiography (TTE) and blood tests. 

Physical examination and cardiac auscultation of a patient with a prosthetic heart valve

Significant abnormal  findings from the physical examination of a patient with a prosthetic heart valve may include a new or changed murmur, muffled valve sounds, or signs indicative of an embolic event (e.g. a neurological deficit in a case of an embolic stroke).
The expected auscultatory findings in patients with a prosthetic valve depend on the type of the valve prosthesis. Normally functioning biological prosthetic valves have the same auscultatory findings as normal native valves. Among the mechanical valves, the bileaflet mechanical valves, which are the type of mechanical valves currently implanted, do not produce an opening sound but only a metallic closing sound. Single-tilting disc mechanical valves produce an opening sound and a closing sound, while the cage-ball valves produce multiple opening sounds, due to the impact of the ball on the cage. On auscultation of the heart, the absence of the expected sounds produced by the prosthetic valves is a pathological finding indicative of limited valve mobility due to thrombosis or tissue hyperplasia.
All mechanical valves in the aortic position additionally produce a characteristic mild systolic ejection murmur. In contrast, the small normal regurgitation of blood (small physiological insufficiency) present in the mechanical valves does not produce a murmur. Therefore, in a patient with a mechanical aortic valve, the finding of a diastolic murmur is a pathological finding, indicating a paravalvular leak (paravalvular regurgitation).

Echocardiography of prosthetic heart valves

The echocardiogram should include measurement of the transvalvular pressure gradient, color Doppler examination to search for a paravalvular regurgitation and assessment of ventricular function.
Echocardiographic findings and measurements within the first few weeks after surgery will serve as a reference for comparison with future findings. A basic parameter is the pressure gradient (pressure difference) across the valve when it is open. The measurement of the peak velocity and the calculation of the peak and mean transvalvular pressure gradient is performed with the continuous wave Doppler. All prosthetic valves have a peak transvalvular velocity which is higher than that of a normal, native valve. They also create a greater pressure gradient than a normal natural valve, given that the latter creates a negligible pressure gradient. As mentioned, depending on the type of prosthetic valve, there are some expected limits for the pressure gradient (some approximate limits have been given above).
Elevated transvalvular velocity and pressure gradient in a prosthetic valve, as compared to the expected values, is observed in cases of: 1) Valve malfunction causing stenosis (thrombus or pannus development, mechanical degeneration and stenosis due to degeneration and calcification of a bioprosthetic valve), 
2) In cases of increased flow through of the valve with no narrowing of the valve (conditions with an increased cardiac output such as hyperthyroidism, anemia or a significant valvular or paravalvular regurgitation). In the case of significant regurgitation at the valve, there is a volume overload of the ventricular cavity located proximally to the valve, resulting in a larger volume of blood passing through the valve when it opens and thus in a higher velocity and pressure gradient.
3) In prosthesis-patient mismatch (PPM), where there is no valve dysfunction, but the valve is small for the patient's body size and circulatory needs. 

Echocardiographic indications of prosthetic valve stenosis

In a prosthetic aortic valve (bioprosthetic or mechanical), indications of a significant stenosis are a peak flow velocity> 4 m / sec, a mean pressure gradient> 35 mmHg, an effective valve orifice <0.8 cm2, and an acceleration time > 100 msec. An indication for a possible stenosis or a moderate stenosis is a peak velocity between 3 and 4, a mean pressure gradient between 20 and 35, an effective orifice between 0.8 and 1.2 and an acceleration time between 80 and 100.  The acceleration time is the time interval between the onset of blood flow through the valve and the peak flow velocity. Apart from the adequacy of valve opening, it is also affected by the heart rate and contractility of the left ventricle. When the shape of the flow signal obtained with the continuous Doppler is triangular with the peak velocity occurring early, this is a sign of normal flow, whereas when it is symmetrical and rounded, this is indicative of stenosis.
In a prosthetic mitral valve (biological or mechanical), a sign of significant stenosis is a peak flow velocity> 2.5 m / sec, a mean pressure gradient ≥ 10 mmHg, 
an effective valve orifice<1 cm2  and a pressure half time (PHT) > 200 msec.
 An indication of a possible stenosis, or moderate stenosis of a prosthetic mitral valve is a peak velocity is between 1.9 and 2.5 / a mean pressure gradient between 6 and 10 / an effective orifice area between 1 and 2 and a PHT between 130 and 200. Apart from valvular function, the PHT is also influenced by left ventricular diastolic function (compliance).

Calculation of the functional orifice area or effective orifice area (EOA) of prosthetic valves 

The functional orifice area or effective orifice area (EOA) of prosthetic valves is calculated with the continuity equation, which is based on the principle that flow in a heartbeat is the same through all areas of the circulation. 
The EOA of a prosthetic aortic valve is calculated with the continuity equation as
CSA LVOT is the cross-sectional area of the LVOT, VTI LVOT the velocity-time integral measured by using pulse wave Doppler in the LVOT, VTI PrAV the velocity-time integral obtained by continuous wave (CW) Doppler through the prosthetic aortic valve. The cross-sectional area of the LVOT is obtained from diameter measurement just proximally to the prosthesis from the parasternal long-axis view.  CSA LVOT = πr= 3.14 x (d/2)2= 0.785 d2,where r is the radius and d is the diameter of the LVOT measured in the parasternal long axis echocardiographic view. Instead of measuring d, the diameter of the sewing ring of the prosthetic aortic valve can be used in this equation as the diameter of the LVOT.
The EOA of a prosthetic valve in the mitral position is calculated as EOA = (CSA LVOT xVTI LVOT )/VTI PrMV,
where VTIPrMV is the velocity-time integral obtained by CW Doppler through the prosthetic mitral valve. 
CSA LVOT = 0.785 d2, where d is the diameter of the LVOT measured in the parasternal long axis echocardiographic view, just proximal to the aortic valve.

Useful videos !! (LINKS)
Assessment of Prostheses in Echocardiography 123sonography (Prof Thomas Binder)

Prosthetic Valve Assessment (William A. Zoghbi, MD) DeBakey Institute For Cardiovascular Education & Training

Prosthetic valve echocardiography 
(Dr. John Chambers, Youtube channel MEDICAL IMAGING)


Prosthetic valve complications

Prosthetic valve thrombosis

There is an increased risk in case of inadequate anticoagulation in a patient with a mechanical prosthetic valve (INR significantly lower than target value) and mechanical prosthetic valves in the mitral position, or the older types of mechanical prosthetic valves (cage-ball, single leaflet). Clinical presentation can be with embolization, e.g. an embolic stroke, or acute limb ischemia, or acute valvular dysfunction causing acute pulmonary edema, or sudden death.
On physical examination diminished intensity of valve sounds may be present. On echocardiography or fluoroscopy, there is a reduced movement of the valve leaflets. There is also an increased transvalvular gradient on echocardiography.
Treatment: Anticoagulation with heparin. If the thrombus is <5 mm on echocardiography, then anticoagulation may suffice. If the thrombus is > 5 mm then apart from heparin, thrombolysis, thrombectomy or valve replacement will be required. Generally for thrombosis of left-sided prosthetic heart valves surgical treatment with valve replacement is indicated, unless there is a prohibitive surgical risk or a small thrombus. For thrombosis of a right-sided prosthetic valve, the treatment of choice is thrombolysis (fibrinolysis). Surgery is indicated if thrombolysis is unsuccessful 24 hours after discontinuation of the infusion.


An embolization in a patient with a prosthetic heart valve more commonly manifests as an ischemic stroke (cerebral infarction).
In patients with prosthetic valves presenting with peripheral embolization, endocarditis should also be considered.
Risk factors include: atrial fibrillation, left ventricular systolic dysfunction, age > 70 years, mitral prostheses, cage-ball valves, the presence of more than 1 prosthetic heart valve. If there are clinical findings suggesting a stroke, a brain computed tomography (CT) should be performed immediately to exclude an intracranial hemorrhage ( in case of an intracranial hemorrhage anticoagulation is withheld and specialist help from a neurologist or neurosurgeon is also needed).

Patient-prosthesis mismatch (PPM)

PPM is a situation where the problem is not prosthetic valve dysfunction, but a small prosthetic valve for patient needs. The effective orifice area (EOA) of the valve is indexed to body surface area (BSA), i.e. it is divided by the BSA. In a prosthetic valve in the aortic position when EOA / BSA0.85 cm2/m2, then there is only mild or no PPM. On the contrary, when EOA / BSA ≤ 0.65 cm2/mthen there is considerable PPM and significant stenotic phenomena. Intermediate values below 0.85 but over 0.65 cm2/m2  suggest a moderate degree of patient prosthesis mismatch (PPM).
In a case of a prosthetic valve at the mitral position, when 
EOA / BSA >1.2 cm2/m2, there is only mild or no mismatch between prosthetic valve and patient. Conversely, when EOA / BSA ≤ 0.9 cm2/m2, then there is considerable PPM and significant stenosis. Intermediate values, below 1.2 but over 0.9 cm2/m2  indicate a moderate degree of PPM.
Several studies link PPM with a decreased postoperative cardiac index, a worse New York Heart Association (NYHA) functional class, a higher likelihood of late adverse events and shorter mean patient survival.

Haemolysis in patients with prosthetic heart valves

A mild haemolysis is common in patients with mechanical prostheses (even with normal prosthetic valve function). Severe haemolysis is not common and is usually a result of prosthetic valve dysfunction (regurgitation, dehiscence, infection).
Blood tests in case of haemolysis show anemia (decreased hemoglobin and hematocrit), increased levels of lactate dehydrogenase (LDH) and reticulocytosis.
Treatment: Administration of folic acid and ferrous sulphate may be needed to increase production of erythrocytes. In severe cases, blood transfusions will be required and identification and treatment of the underlying problem (including valve replacement for cases requiring frequent blood transfusions).

Prosthetic valve endocarditis

Early prosthetic heart valve endocarditis (≤ 2 months after implantation) is usually caused by staphylococcus epidermidis and often presents as acute endocarditis with a fulminant clinical course and high mortality rates (>20%). Late prosthetic valve endocarditis is usually caused by microorganisms that are the usual pathogens in native valve endocarditis, such as streptococci which are the most common causative agents, followed by gram negative bacteria and enterococci.
The imaging modality of choice is transesophageal echocardiography (TEE) which can detect vegetations, or complications of prosthetic valve endocarditis, such as valve dehiscence or an abscess.

Paravalvular leak

It is the regurgitation of blood in an area just next to the sewing ring of the valve, due to a poor contact of the valve with adjacent tissues to which it has been sutured. Possible causes include an infection (endocarditis), calcification or fibrosis of the native valve annulus, resulting in poor contact with the suture ring, or suture detachment. In patients with a mild (small) paravalvular leak, the prognosis is good and only periodic follow up is required. In a severe paravalvular leak that causes symptoms, significant hemolysis, or left ventricular dilation due to volume overload, surgical or transcatheter management is required. A paravalvular leak is more common with transcatheter aortic valve implantation (TAVI) than with surgical implantation of a prosthetic valve.

Prosthetic valve dehiscence

Dehiscence (detachment) of the prosthetic valve suture ring from the valve annulus may occur in the early postoperative period due to surgical errors, the presence of extensive calcification of the valve annulus, infection (endocarditis), fragile valve annular tissue due to previous surgery, or chronic corticosteroid use. Late dehiscence of a prosthetic valve is due to infectious endocarditis. An indication of valve dehiscence is an abnormal rocking motion of the prosthetic valve in echocardiography or fluoroscopic examination. Dehiscence is an indication for emergency surgery.

Prosthetic heart valve structural degeneration

Bioprosthetic valves, as opposed to mechanical valves, have the advantage of being less thrombogenic, but they also have the disadvantage that they develop degenerative lesions over the years (thickening and/or calcification with progressive stenosis or regurgitation). Factors associated with increased risk for a patient to develop degenerative lesions in a bioprosthetic valve are young, age, a bioprosthetic valve in the mitral position, renal failure, and hyperparathyroidism. The most common cause of malfunction of a bioprosthetic valve is the structural degeneration of the valve.


Zoghbi, WA, et al. Recommendations for Evaluation of Prosthetic Valves With Echocardiography and Doppler Ultrasound. Journal of the American Society of Echocardiography 2009;22: 075-1014.

Baumgartner H, et al. 2017 ESC/EACTS Guidelines for the management of valvular heart disease: The Task Force for the Management of Valvular Heart Disease of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS), European Heart Journal, ehx391,

Chambers JB. Prosthetic heart valves. The International Journal of Clinical Practice 2014; 68:1227-1230 LINK

Bajaj RKarthikeyan G, et al.CSI consensus statement on prosthetic valve follow up. Indian Heart Journal 2012; 64: S3 -S11 LINK

Habets, J. et al. Diagnostic evaluation of left-sided prosthetic heart valve dysfunction Nat. Rev. Cardiol 2011;8: 466-478.

Huang G1, Schaff HV, et al. Treatment of obstructive thrombosed prosthetic heart valve.J Am Coll Cardiol. 2013 ;62:1731-1736.

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

Bibliography and links 

Baumgarther H, et al. 2017 ESC/EACTS Guidelines for the management of valvular heart disease: The Task Force for the Management of Valvular Heart Disease of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS), European Heart Journal, , ehx391,

EAE/ASE: Echocardiographic assessment of stenotic heart valves (A very useful guideline in slides)

Wickiecho: Pulmonary stenosis

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. (Normally the right ventricular wall is thinner and more compliant than the left ventricular wall. Right ventricular wall thickness in diastole can be measured in the subxiphoid echocardiographic view. Normally it is < 5 mm). A practical assessment of the right ventricular size is obtained by its comparison with the size of the left ventricle in the apical four-chamber view. Normally the right ventricle( RV)  should be less than two-thirds of the size of the left ventricle (LV). However, this may be misleading when LV dilation coexists.
(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 

Guazzi M1, Galiè N., et al. Pulmonary hypertension in left heart disease. Eur Respir Rev. 2012;21:338-46. doi:10.1183/09059180.00004612.

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

Rudski LG, Wyman WW et al.Guidelines for the Echocardiographic Assessment of the Right Heart in Adults: A Report from the American Society of EchocardiographyJ Am Soc Echocardiogr 2010;23:685-713