What is Valvular Heart Disease
Normally, when the leaflets of the valve close, they stay shut. This ensures the circulation through the heart in one direction only. However, when a valve is insufficient /leaking it does not stay closed, allowing the blood to travel in the wrong direction or backwards which is called regurgitation.

These two valvular dysfunctions (stenosis and insufficiency) can occur in isolation or simultaneously to anyone of the heart valves. Sometimes more than one valve is affected and requires repair or replacement.

Your surgeon will decide what will be the best for long term result i.e. to replace or to repair the valve. Valve repair has the advantage of limination of long term anticoagulation (blood thinner) with the disadvantage of again failure due to continued disease process.

Valve Replacement: There are two types of artificial heart valves that can be used to replace original valves, biologic (tissue) & mechanical (metal alloy).

The Biological Valve: The biologic or tissue valves are mainly made of pig valves, or pig pericardium [allograft / xenograft] or human valve [Homograft]. These biologic valves tend to calcify and are less durable. After 10 years some 60% need to be replaced. Human valve tissue Homografts have the inherent disadvantage of limited availability and are expansive.

These new generation advanced bio-prostheses are procured with highest quality control process. Now a days genetically engineered, cryopreserved, antibiotic sterilised bio-protheses are available to make them last long with out degeneration. These are particularly useful in young females and elderly people above age of seventy years and in patients in whom long term anti coagulation (blood thinning) is medically contraindicated.

Mechanical valves are made up of synthetic materials: Metal alloys (Titanium, pyrolite carbon) various plastics (high density polypropylene) etc., They come in three major designs.

One is called caged ball valve, the second consists of a round disc (pivoting inside a ring) in which tilts to a horizontal or vertical position to let the blood flow through or prevent its flow. The third one consists of two half round disks (bileaflet valve)
and are latest modifications.






The Mechanical Valve: Mechanical valves are more durable than biologic (Tissue) valves and last longer. They do, however, tend to promote abnormal clot formation on their surface, so in order to keep them properly functioning, patient must take anticoagulation (blood thinner) drugs as a preventive measure to keep blood thin. These drugs (WARFARIN, ACENOCOUMARIN) may be prescribed along with or with out anti platelet drugs (Dispirin) to make your blood thinner than normal. This is a preventive measure to avoid clot formation on the surface of newly implanted mechanical valve. These blood thinner drugs have to be taken life long.







Prothrombin Time [PT] Test: This is a blood investigation which determines blood thinness and depending upon the result, dosage of blood thinner (Warfarin, acinocouomarin) is decided accordingly. This test has three readings :

• The control: (Blood Thickness, development time). Normal Subject Reading.
• The Test: Patient's Reading.
• The INR (International Normalised Ratio) : Which is Comparision ratio of standard between Control & Test (Normalised). This is usually kept twice or thrice [meaning test number higher than control] by proper drug dosage given by qualified physician to keep your blood adequately thin and prevent clot formation.

Management of Anticoagulation:

INDICATIONS FOR ORAL ANTICOAGULATION THERAPY: Thrombosis and its complications involve many organ systems in the body and long term oral anticoagulation has been tried as therapy of these diorders. Over the last 5 decades, several controlled trials for use of oral anticoagulants with or without anti platelet agents for various disorders have given us insight into and guidelines for oral anticoagulation therapy. The major indications for the use of long term anticoagulants are as follows:

CARDIOVASCULAR CONDITIONS

1. Preventing thromboembolism in patients with prosthetic heart valves.
2. Preventing systemic embolism in patients with atrial fibrillation.
3. Deep vein thrombosis.
4. Preventing systemic embolism in patients with abnormal ventricular functions.
5. Paradoxical embolism.
6. Severe pulmonary hypertension due to chronic recurrent pulmonary thromboembolism.

CEREBROVASCULAR CONDITIONS

1. Transient ischemic attack.
2. Extracranial major vessel dissection.
3. Cerebral venous disorders in the setting of prothrombotic disorders/states.

CARDIOVASCULAR CONDITIONS

Preventing thromboembolism in patients with prosthetic heart valves: Systemic embolism remains a complication in patients following heart valve replacement. Oral anticoagulation therapy reduces the rate of this serious complication from 5 to 50% to 1 -3% per year. Based on several trials addressing the issue of intensity of anticoagulation, duration of anticoagulation and combination of anti platelet agents with anticoagulants, the following guidelines seem to be the most optimum.

Anticoagulation therapy for prosthetic valve
Type of valve	Antithrombotic therapy	Duration
Mechanical Valve
Mechanical prosthetic valve	Warfarin or Nicoumalone Target INR 2.5 to 3.5	life long
Mechanical valve + Systemic embolism / dilated LA/depressed LV function / chronic AF	As above + Aspirin 100-160 mg per day or Dipyridamole 100 mg TDS	life long
Mechanical Prosthetic valve and high risk of bleeding	Warfarin or Nicoumalone Target INR of 2-3	life long
Tissue Valve
Bioprosthetic (mitral or aortic)	Warfarin or Nicoumalone Target INR of 2-3	3 months
Bioprosthetic + Chronic AF or atrial thrombus	As above	long term
Bioprosthetic with system embolism	As above	1 year
Uncomplicated bioprosthetic after first 3 months	Aspirin 325 mg per day	life long

Preventing systemic embolization in patients with atrial fibrillation (AF): The risk of systemic embolization in patients with artrial fibrillation have been long recognized and has been attributed to left atrial enlargement with stasis. The absolute annual rate of stroke is identical in patients with rheumatic and nonrheumatic AF and approaches 4.5%. The consequences of embolic stroke are devastating and as many as 50 to 70% of these result in severe neurologic deficit or death. The annual risk of stroke among patients with nonrheumatic AF changes depending on the presence or absence of clinical risk factors (these include CHF, hypertension and previous systemic embolus) and echo cardiographic risk factors (which include LAE and LV dysfunction).

Annual risk of stroke among patients with nonrheumatic atrial fibrillation according to baseline clinical and echocardiographic characteristics.
Characteristics	Annual Risk %
No clinical risk factor*	2.5
No echocardiographic risk factor@	1.0
1 or 2 echocardiographic risk factors	5.0
1 clinical risk factor	7.2
2 or 3 clinical risk factors	17.6
Age 60 yr. no clinical risk factor	0
Any age, no clinical risk factor, no diabetes	1.4

*Clinical risk factor means recent congestive heart failure, history of hypertension or previous systemic embolus.
@Echocardiographic risk factor means left atrial enlargement or left ventricular dysfunction.

The results of clinical trials of antithrombotic therapy in patients with chronic AF can be summarized as follows:

• Warfarin therapy (INR 2 to 3) results in the prevention of 31 strokes per year for every 1000 patients treated at a cost of three major bleeds per year (inlcuding cerebral hemorrhage).
• The risk of stroke is highest among patients with hypertension, previous cerebral embolus, a history of congestive heart failure, and an echocardiographically enlarged left atrium or left ventricular dysfunction. Diabetes mellitus also appears to be a predictor. The greatest absolute benefIts of warfarin therapy are likely to be observed among such patients. The risk of stroke is very low among patients with one atrial fibrillation, and warfarin therapy is not justified.
• The relative and absolute benefits of warfarin appear to be particularly high among patients with previous transient ischemic attacks or minor storke.
• Aspirin therapy results in the prevention of about 15 to 20 strokes per year for every 1000 patients treated at a cost of major bleeding that is probably less than that for warfarin.
• The risk of major hemorrhage is particularly high in the very elderly and may counteract the potential benefits of warfarin. Further trials are evaluating lower dose warfarin and aspirin.

Deep venous thrombosis: Deep venous thrombosis (DVT) is the underlying cause of both pulmonary embolism (PE) and chronic venous insufficiency of legs. As most DVT is unrecognized, the true frequency is much higher. Overall about one third of DVTs are recurrent events. Upper extreimity DVT seems to be increasing because of widespread use of central venous catheters.

Theraphy of DVT should be based on:

• Anatomic extent of thrombus
• Patient's risk of PE
• First vs. recurrent DVT
• Chronic venous insufficiency
• Idiopathic vs. secondary DVT

All these need variable duration oral anticoagulation with a target INR between 2 & 3.

Target INR in DVT of leg.
Type of DVT	Target INR	Duration
Isolated calf	2-3	3 months
Proximal leg or upper exteremity DVT	2-3	6 months
Recurrent DVT	3-4	12 months

Note: Idiopathic DVT's need to be treated longer than secondary DVT's as per the clinician's judgement.

In all idiopathic DVT's the following workup is recommended:

• Protein C level (activity and antigen)
• Protein S level ('free' Protein S antigen and activity)
• Antithrombin III level (activity and antigen)
• Workup for occult malignancy
• Tests for lupus anticoagulant/anticardiolipin antibody
• Activated Protein C resistance/Factor V Leiden
• Fibrinogen level
• Factor VIII level
• Serum homocystein

Blood sample for the above tests must be collected before starting anticoagulation therapy.

Preventing systemic embolism in patients with abnormal ventricular function: Preventing system embolism in patients with abnormal ventricular function is effective and safe and is indicated in following circumstances:

• Large anterior infarction (annual embolism incidence 4.5 -14%)
• Left ventricular mural-thrombi (annual incidence of embolism 20%)
• Left ventricular aneurysm (annual incidence of embolism 4-5%)
• ilated cardiomyopathy (annual incidence of embolism 4-5%)
• Cardiac myxomas (overall incidence of embolism 50%)

Target INR and duration of anticoagulation in patients with left ventricular dysfunction.
Indication	Target INR	Duration
Large anterior infarction	2-3	6 months
Left ventricular mural thrombus	2-3	Till echcardiographic resolution of thrombus
Dilated cardiomyopathy	2-3	Life long or until definitive therapy such as cardiac transplant
LV aneurysm	2-3	Life long or until definitive therapy such as aneurysmectomy
cardiac myxomas	2-3	Until 3 motnhs post-operatively after surgical removal of myxomas

Patients with paradoxical embolism: Among patients with cryptogenic stroke, paradoxical embolism to the brain is causative more often than suspected. In one study in patients with cryptogenic storke contrast TEE identified PFO in 18% and out of these 57% had venographic evidence of DVT particularly restricted to calf veins. Thus in patients with stroke with echo evidence of PFO with or without definite evidence of DVT one-year therapy with oral anticoagulants with a target INR of 2-3 is recommended.

Patients with severe pulmonary hypertension due to recurrent pulmonary thromboembolism: In patients presenting with clinical and echocardiographic features of severe pulmonary hypertension, one third are found to have chronic pulmonary embolism on vIa scan. These patients merit life long oral anticoagulation with a target INR between 1.5 ot 2.5 with low dose of Aspirin 50-70 mg/day.


CEREBROVASCULAR CONDITIONS

1. Transient ischemic attacks (T1As) : It is reasonable to use oral anticoagulant in persons whose TIAs are not controlled with blood pressure optimisation and asprin or ticlopidine. A target INR of two should be adopted. At times, crescendo TIAs (TIAs with increasing frequency. symptoms severity or symptom repertoire) and visual TIAs may demand oral anticoagulant therapy. Persons with high-grade extracranial vascular stenosis (e.g. internal carotid artery stenosis > 70%) associated with appropriately localised TIAs who are not agreeable to intervention, may also be a group in whom oral anticoagulant may be considered.
2. Extracranial major vessel dissectin: Persons in this group, who have had their lesions documented with vascular imaging methods are usually placed on oral anticoagulant therapy for a period of approximately 3 months by which time intimization is assumed to have occurred. A target INR of 2 should again be considered.
3. Cerebral venous disorders in the setting of prothrombotic disorders/states: As already mentioned, perosns in this group should have their disorders clearly outlined by available mehtods of assay (e.g. protein SIC deficiency, activated protein C resistance, antithrombin III deficiency etc.). Following this, it is reasonable to advise oral anticoagulation with a target INR of 2.

MONITORING OF ORAL ANTICOAGULATION: In most clinical situations warranting oral anticoagulation (see above), the therapy is continued over a long period of time. To avoid risks of over -and under -anticoagulation of the patient a close monitoring of the INR is mandatory. This could be achieved by observing the following guidelines:

1. Determine the baseline Prothrombin Time (PT)/INR before starting the therapy.
2. Daily determination of PT/INR is necessary till the desired level is attained. Fortnightly to monthly evaluation is desirable thereafter. In patients with stable PT/INR, assay could be repeated every 2 months.
3. If the dose of the oral anticoagulant needs to be changed for any reason or if any other drug needs to be added or omitted, INR must be done following such a change in therapy.
4. INR should be determined every time by the same laboratory using the same method.
5. It is advisable to give the dose of the oral anticoagulant in the evening and measure the INR the next morning.
6. A fasting sample is preferable for monitoring of INR. Most laboratories use optical or opticomechanical technique for determination of PTIINR. Hence, a lipemic plasma could affect the outcome of the test.
7. Ensure proper collection of blood sample through a clean venepuncture. Presence of blood clot in the sample, altered ratio of blood to the anticoagulant and excessive frothing of blood can affect the PT/INR.
8. Ensure that the laboratory uses a mean normal PT (MNPT) and not the PT of a single control sample for calculating INR.

FACTORS INFLUENCEING PT/INR: In addition to the individual variations in the capability of metabolising oral anticoagulants, a host of other patient-related factors influence the in vivo kinetics of these drugs, resulting in instability of INR even on a fixed dose of the drug. These include:

• Low body weight
• Old age
• Variable dietary intake of vitamin K
• Non-compliance
• Abnormal liver function
• Presence of cardiac failure
• Parenteral feeding
• Drug interactions (see below)
• Pharmacokinetics of the anticoagulant.

DRUG INTERACTIONS: Awareness of drug interactions in an essential prerequisite for starting oral anticoagulation therapy since majority of cases of highly fluctuating PT/INR encountered in practice are due to concomittant ingestion of drugs which (a) compete with oral anticoagulant for binding with plasma proteins and/or (b) influence the activity of hepatic microsomal enzymes, thereby ­altering the rate of metabolism of oral anticoagulants. The following durgs are know to alter anticoagulant effect of Warfarin:

Drugs which increase the anticoagulant effect of warfarin/acchocoumarin:

• Alcohol
• Antibiotics ( cephalosporins, penicillin, sulphonamides, tetracyclines)
• Anti-inflammatory analgesics (aspirin, indomethacin, phenylbutazone)
• Oral hypoglycaemic agents (tolbutamide, chlorpropamide, phenformin)
• Anti-hyperlipidaemic agents (clofibrate, cholestyramine)
• Antidespressants (tricyclic antidepressants, phenothiazines)
• Anabolic steroids
• Allopurinol
• Laxatives
• Glucagon
• Quinine
• Thyroxine

Drug which decrease the anticoagulant effect of warfarin:

• Barbiturates
• Phenytoin
• Glutethimide
• Spironolactone
• Rifampicin
• Griseofulvin
• Haloperidol
• Oral contraceptives

If any of the abovementioned drugs must be used in patients on oral anticoagulation, the following steps are necessary to avoid bleeding complications or to ensure optimal anticoagulation:

1. Explain the rationale of anticoagulation therapY to the patient. He should also be cautioned against alteration of the dose of medications and additions/subtraction of drugs without discussing the same with his physicians.
2. Closer monitoring of PT/INR till the same is in the desired therapeutic range and is stable over atleast a fortnight or so.

MANAGEMENT Of BLEEDING DUE TO EXCESSIVE ANTICOAGULATION:

• Patients on oral anticoagulants have a significant risk of bleeding at INR > 5. Recommendations for management of bleeding due to excessive anticoagulation are listed in Table below.
• Immediately check PT/INR in the event of bleeding. Stop oral anticoagulation only if the PT/INR is unacceptably high. Bleeding in patients on oral anticoagulation could be due to a local cause without increase in PT/INR beyond the desired therapeutic level. Hasty stoppage of oral anticoagulation under these circumstances could be disastrous.

Recommendations for management of bleeding due to excessive anticoagulation.
> 3.0 INR < 6.0 target INR 2.5	reduce warfarin dose or stop
> 4.0 INR < 6.0 target INR 3.5	restart warfarin when INR < 5.0
> 6.0 INR < 8.0 no bleeding or minor bleeding	stop warfarin restart when INR < 5.0
INR < 8.0 no bleeding or minor bleeding	1. stop warfarin 2. restart when INR < 5.0 3. if other risk factors for bleeding give 0.5     - 2.5 mg of vitamin K (oral)
major bleeding	1. stop warfarin 2. give prothrombin comlpex concentrate     50 units/kg or FFP 15 ml/kg 3. give 5mg of vitamin K (oral or i.v.)

• Fresh frozen plasma infusion could be life-saving in cases of serious bleeding complication as a result of overanticoagulation since even parenteral vitamin K could take 48-72 hrs to act.

Prevention of Infection: As with any kind of body infection, bacteria can enter into the blood stream and traverse to lodge on inner lining of artificial valve. Causing a condition called prosthetic endocarditis, which is difficult to eradicate. So do not allow any infection to set in your body.

• Watch for any unexplained fever and should you catch sore throats, it should be promptly and aggressively treated.
• Avoid visiting known places of infection (filthy places) .Avoid drinking unsafe, drinking water.
• Avoid taking un-hygienically cooked or stale food.
• Personal body hygiene and cleanliness particularly oral hygiene is very important. Clean your teeth gently and properly. Any loose tooth or oral cavity tooth infection or body infection (boils etc.,) should be aggressively treated and prompt attended.

Medical Identification: It is important that you carry an identification card stating your name, blood group, antocoagulation drug and your physician's name to be contacted in emergency.