Transcatheter Aortic-valve Implantation, abbreviated as TAVI, is a minimally invasive surgical procedure intended to better regulate the flow of blood through the aortic valve that bridges between the heart and the aorta. This newly developed procedure is designed to suit the needs and demands of a high-risk population of patients for whom the traditional valve replacement surgery presents with fatal risk factors (American Heart Association, 2014).

Structure of the Heart

Sourced from http://labspace.open.ac.uk/file.php/

The human heart is a muscular organ comprising of four chambers - two atria and two ventricles. The heart's function in our body can be grouped into two major classes of circulation - systemic and pulmonary circulation. The systemic circulation serves the body’s tissues with oxygen-rich blood and collects the deoxygenated blood from those tissues. The pulmonary circulation involves the circulation of blood between the lungs and the heart. The systemic loop of circulation begins when the left atria of the heart receives oxygenated blood from the lungs carried by the pulmonary vein. The collected blood is then dispersed to the body’s tissues and organs through pumping it out from the left ventricle. The aorta is the principal blood vessel that collects the oxygen-rich blood pumped out from the left ventricle and disperses it across the various tissues and organ systems in the human body by branching out into arteries and capillaries.

On the other side, the right atria collects the deoxygenated blood brought in by the inferior and superior vena cava from the body’s tissues and pumps it from the right ventricle to the pulmonary artery which carries it to get oxygenated from the lungs. In the movement of blood between the atria and ventricles, the blood passes through two valves including the tricuspid valve on the right side, and the bicuspid (mitral) valve on the left side of the heart. These valves are called atrioventricular valves or AV valves.

Overall, the left side of the heart specializes in systemic circulation and the right side focuses on pulmonary circulation. Once the blood leaves the ventricles into the blood vessels, it passes through a second set of valves called semilunar valves. The semilunar valve between the left ventricle and aorta is names the aortic valve and that connecting the right ventricle to pulmonary artery is called pulmonary valve. These valves regulate the blood flow in the heart to follow a designated direction of flow (Latent Semantic Analysis, 2014).

A schematic of the circulatory system illustrating the pulmonary circulation picking up oxygen from the lungs and the systemic circulation delivering oxygen to the body.

Sourced from biology-forums.com

The aortic valve is a semilunar valve with three cusps, that regulates the entry of blood from the left ventricle into the aorta following a ventricular systole. It is largely a pressure regulated valve as it opens when the ventricle is filled with blood. As its blood pressure increases beyond the aortic pressure, the aortic valve opens to allow blood to empty into the aorta. When the aortic pressure builds up and rises above that of the ventricular pressure, the aortic valve closes in response (Latent Semantic Analysis, 2014).

Aortic Valve

Sourced from B.C. Decker

The cardiac valve has two primary functions by opening and closing. When opening, the cardiac valve controls the direction in which the blood flows. When closing, the cardiac valve controls the pressure differentials by making it a closed system. Abnormal valve function therefore produces either pressure overloading or volume overloading (Zigelman et al., 2009).

Aortic valve disease is a condition where the valve between the left ventricle and the aorta does not function properly. It is subdivided into two categories depending on whether poor opening or closing is occurring. Thus, aortic valve diseases are diagnosed as aortic valve stenosis and aortic valve regurgitation.

Aortic valve stenosis is a disease of the heart valves in which the opening of the aortic valve is restricted or narrowed. Together, when the blood flowing out from the heart is trapped by a poorly functioning valve, pressure may build up inside the left ventricle and cause damage. To understand the term better, stenosis in ancient greek means narrowing. AVS is primarily a disease acquired in elderly patients. About 1-2% are born with what is known as a bicuspid aortic valve that is known to frequently evolve into stenosis (Roberts, 1970). A normal aortic valve has three leaflets or cusps, known as a tricuspid. Patients who develop AVS principally undergo the 3S Rule: shortness of breath, syncope and sudden death (Zigelman et al, 2009).

AVS progresses due to cuspal calcification, often requiring valve replacement surgery. The mechanisms that cause the cuspal mineralization are not fully understood (Jian et al., 2003). Many previous studies suggest different theories. One group believes that the appearance of apoptotic vesicles involvement early on causes this calcification. Another prominent theory is the presence of extracellular matrix proteins typically found in bone as a result of excess blood present (Srivatsa et al., 1997). One new hypothesis that ties all the previous theories is currently being found in the literature. That is, TGF-beta1, a cytokine known for calcification of smooth muscle senses the increased blood volume by protease activity in the blood and contributes to the progression of calcification in AVS (Jian et al., 2003).

Aortic stenosis is the most frequent reason for valve interventions in North America and Europe. Echocardiography is the key diagnostic tool for diagnosis, quantification, stenosis severity and assessment of secondary changes. Patients with key symptoms such as: dyspnea, angina, dizziness/syncope with exertion will require urgent surgery. A lof of patients are asymptomatic so regular echocardiographic and clinical examinations by doctors should be implemented.

Aortic valve replacements serve to achieve three main goals including: maintaining adequate blood flow, ensure durability with increasing age, and limit the risk of thrombosis (Wernly, J. A., & Crawford, M. H, 1998). The two major designs of aortic valves are mechanical, and biological tissue valves. Each type of valve possess advantages over the other, but both serve identical purposes. The decision to select the type of valve depends on numerous factors which will be discussed.

Mechanical valves generally predominate as the leading replacement method in the United States compared to biological tissue valves (Wernly, J. A., & Crawford, M. H, 1998). Numerous types of mechanical valves have been made, each differing in size, mechanical functionality, and placement within the heart ((Wernly, J. A., & Crawford, M. H, 1998). For instance, the Starr-Edwards Valve was the first mechanical valve manufactured in the mid-20th century. It was relatively easy to insert, but the large size limited its use in patients with small left ventricles, or narrow aortas (Wernly, J. A., & Crawford, M. H, 1998). Since the first mechanical valve, there have numerous variations and developments of mechanical valves in attempt to mimic the human valve.

Mechanical valves are produced with non-biological materials including polymer, carbon, and metal (Schoen, F.J, and Levy, R. J., 1999).In comparison, tissue valves are generally synthesized from porcine or bovine tissue (Schoen, F.J, and Levy, R. J., 1999). Although both are designed to perform the same function, they both present various types of limitations, and benefits.

Patients with mechanical valves are highly susceptible to systemic thromboemboli which entails clotting of the blood. This is believed to occur due to the rigid nature of the mechanical valve and thus creates abnormal blood flow (Schoen, F.J, and Levy, R. J., 1999). Patients can reduce this risk with the use of anticoagulants such as warfarin and aspirin (Schoen, F.J, and Levy, R. J., 1999). However, patients must continue taking blood thinners for the remainder of their life to avoid complications. Nevertheless, mechanical valves are generally preferred because they offer lifetime durability, with very few or zero structural compromise (Schoen, F.J, and Levy, R. J., 1999). This is due to the increasing efforts to engineer valves from very strong materials.

Tissue valves generally have low risk of thrombosis as its material is composed of animal tissue, not metal and other non-biological material (Schoen, F.J, and Levy, R. J., 1999). This substantially reduces the risk for blood clotting and eliminates the need for anticoagulants (Schoen, F.J, and Levy, R. J., 1999). However, the lifetime of tissue valves is significantly less as compared to mechanical valves. Tissue valves undergo gradual deterioration with age ( Schoen, F.J, and Levy, R. J., 1999). The first decade after implantation is virtually-free of structural failure. However, the structural integrity of the valve is severely compromised after this, and could result in serious complications later in the patient’s life (Schoen, F.J, and Levy, R. J., 1999). Although tissue valves have very low risk of thrombosis, and patients do not require anticoagulation, its durability poses a serious risk to the patient (Schoen, F.J, and Levy, R. J., 1999).

The TAVI procedure is performed with the use of the Edwards Sapien Transcatheter Heart Valve (THV), which is an artificial heart valve designed to hold open and replace the diseased aortic valve (National University Heart Centre, 2009). This is a surgical procedure which is minimally invasive, in which the valve is repaired without the need to remove the old impaired valve (American Heart Association, 2014). Instead, this procedure inserts a replacement valve into the place of the original aortic valve. This procedure works similar to the procedure of placing a stent in an artery. The THV is made from a metal stent (steel or cobalt-chromium), which functions to secure the device in the position of the diseased valve. The THV also consists of valve leaflets, which are produced from biological material derived from bovine (National University Heart Centre, 2009). The TAVI method involves delivering the fully collapsible replacement valve to the site of the damaged valve through a catheter (American Heart Association, 2014). Once the new valve is in place, it expands, and pushes the leaflets of the old valve in an outward direction (American Heart Association, 2014). The tissue in the new replacement valve takes over and regulates the flow of blood, similar to a healthy patient.

Edwards SAPIEN 3 Transcatheter Heart Valve.

Sourced from Edwards Lifesciences Corporation, 2014

There are generally two approaches patients can undergo for TAVI treatment including: transfemoral and transapical TAVI. The method chosen for a patient will provide the safest approach to access the damaged valve specific to the patient.

A)Transfemoral TAVI

The transfemoral approach involves the device to be implanted through a large artery in the groin area, known as the femoral artery in a retrograde fashion. It is referred to as the transfemoral approach because it does not entail a surgical incision into the chest area. Because of the size of the catheter (a hollow tube) that will need to go through the femoral artery, doctors generally assess angiograms and CT scans too ensure the artery is large enough to withstand the device (National University Heart Centre, 2009). Prior to implantation, the THV is “crimped”, which means that it is compressed to a smaller size to fit inside the femoral artery (National University Heart Centre, 2009). The crimped THV is then attached to a balloon delivery catheter, which is a device that carries the THV up to the aortic valve in the heart (National University Heart Centre, 2009). The stenotic aortic valve is then expanded using a balloon, pushing the defective leaflets outward, and is now held open permanently (National University Heart Centre, 2009). Once the new THV is in place, and the delivery system catheter is removed from the femoral artery, the artery is sutured closed.

Transfemoral Approach where catheter is inserted through the femoral artery.

Sourced from National University Heart Centre, 2009

B) Transapical TAVI

The transapical approach is an alternate approach to the transfemoral approach. This approach is used mainly for patients whose femoral arteries are not large enough for the transfemoral method. This approach is a minimally invasive surgical approach which involves a small incision in the chest. The catheter is inserted through a large artery in the chest or through the apex, which is the area at the tip of the left ventricle (National University Heart Centre, 2009). The apex is reached through a minute slit made between the ribs. The THV (in crimped form) and balloon delivery system is inserted through the apex and directly into the defective aortic valve (National University Heart Centre, 2009). The valve is then expanded using a balloon and held open permanently, as the THV is positioned into place (National University Heart Centre, 2009). The THV then takes over the function of regulating blood flow as a healthy aortic valve should. Because the heart is not cut open in either of these approaches to expose the aortic valve, fluoroscopy X-rays and transesophageal echocardiography (ultrasounds) are relied upon in order to visualize the heart and THV (National University Heart Centre, 2009). This is extremely important to safely guide the insertion of the THV.

Transapical Approach where catheter is inserted through the apex of the heart.

Sourced from National University Heart Centre, 2009

TAVI is a fairly recent procedure, which has been FDA approved for patients with conditions, such as symptomatic aortic stenosis. This method is also more relevant and targeted for patients at high risk for the standard valve replacement surgery (American Heart Association, 2014). TAVI differs from standard valve replacements because normally, valve replacements require a surgeon to conduct a sternotomy, where the chest is surgically cut open for the procedure (American Heart Association, 2014). However, the TAVI method can be conducted by simply producing very small openings, rendering the chest bones intact. Thus, TAVI does not require a bypass, and is not considered open-heart surgery. Another advantage of TAVI is there is a shorter recovery period after the proecedure. A patient’s experience with a TAVI is similar to an angiogram, in regards to the recovery time (American Heart Association, 2014). This includes a shorter hospital stay of about 3-5 days.

The TAVI technique is relatively new to the scientific community, and thus this procedure is mainly reserved for patients who are unable to go through the standard open-heart approach because they are high risk patients. Therefore, procedures are generally performed on patients who are in their 70s and 80s, and have comorbid conditions (American Heart Association, 2014).

Generally patients are prescribed anticoagulants such as Aspirin and Plavix (University of Ottawa Heart Institute, 2012). These medications are blood-thinners, working to make the blood less sticky and preventing thrombosis in the new valve. Routine checks will also be completed at the hospital during the recovery. These include physical examinations, blood tests, chest X-rays, daily electrocardiograms (ECGs), and transthoracic echocardiograms (TTEs) (National University Heart Centre, 2009). It is also required to have clinical visits to the doctors periodically to check for abnormalities (National University Heart Centre, 2009).

Replacement Valve Risks

Similar to all types of operations, there are still some risks involved in the TAVI procedure. Anticoagulation must be monitored closely and severe blood thinning can increase the risk of excess bleeding (American Heart Association, 2014). Some risks of the TAVI procedure include (National University Heart Centre, 2009):

• Hemorrhage (bleeding) requiring transfusion (0.1 – 5%)
• Abnormal heart rhythms (0.1 – 25%)
• Heart or blood vessel injury, such as perforation or damage of blood vessels, heart muscle valve structures that may require emergency surgery (1 – 10%)
• Heart attack or stroke (1 – 10%)
• Infection including valve infection (0.01 – 1%)
• Hypertension (high blood pressure) / Hypotension (low blood pressure) (0.1 – 5%)
• Death (1 – 10%)

A study conducted by Gotzmann and colleagues aimed to determine the extent of improvement in certain clinical symptoms, as well as neurohumoral activation in patients who have undergone the TAVI procedure . In this study, 44 consecutive patients who had severe and symptomatic aortic valve stenosis (characterized by having an aortic valve area of less than 1cm2) underwent the TAVI procedure (Gotzmann et al., 2014). The mean age of the chosen patients was 79.1 years and was composed of 50% men and 50% women (Gotzmann et al., 2014). In order to choose which patients qualified for the TAVI procedure, they had specific selection criteria (Gotzmann et al., 2014).

The patients were chosen based on the following criteria:

• Symptomatic, severe aortic valve stenosis→ aortic valve area <1cm2
• Aortic annular dimensions between 20mm and 27mm and an ascending aortic diameter <45mm
• Age: >75 years with a greater than 15% risk of standard surgical aortic valve replacement. If >60 years with at least one other specific risk factor (liver cirrhosis, respiratory

failure previous cardiac surgery, pulmonary hypertension and a few others)

Examinations of the subjects were done before the TAVI procedure, as well as 30 days after the TAVI. The examinations comprised of assessing their quality of life (via the Minnesota living with heart failure questionnaire—MLHFQ), a 6-minute walk test, and a measurement of B-type natriuretic peptide to study neurohormonal activation after TAVI (Gotzmann et al., 2014). The transcatheter aortic valve implantation was done using the transfemoral approach (through the femoral artery). Clinical investigations of patients were performed within 7 days before TAVI and 30 days after TAVI (Gotzmann et al., 2014).

The “Minnesota Living with Heart Failure Questionnaire” is a standard questionnaire designed to measure of the effects of heart failure and treatments for heart failure on an individual’s physical, social, emotional and mental aspects of their quality of life (Gotzmann et al., 2014). Each of the responses score was summed, leading to the total MLHFQ score for each patient. The test can range between 0 and 110, in which higher scores signify a poorer quality of life. The baseline MLHFQ score was 44 ± 19.1 (Gotzmann et al., 2014). The follow-up 30 days after TAVI showed a drastic improvement in the quality of life, in which the score was 28 ± 17.5 (Gotzmann et al., 2014).

Minnesota Living with Heart Failure Questionnaire used to assess the quality of life after TAVI procedure

Sourced from Gotzmann et al., 2014

This test was conducted based on the guidelines of the American Thoracic Society. The subjects were ordered to walk briskly for a time of 6 minutes or until signs of dsypnea or muscular fatigue emerged. The total walking distance for each subject was recorded in metres. The baseline distance recorded for this walking test was 204 ± 103m (Gotzmann et al., 2014). After the TAVI procedure was conducted, an enhanced distance in the 6-minute walk test was observed, at a value of 266 ± 123m (Gotzmann et al., 2014).

6-Minute Walk Test used to assess functional capacity after TAVI procedure.

Sourced from Gotzmann et al., 2014

This test was conducted to study the neurohormonal activation in patients after the TAVI procedure. B-type natriuretic peptide (BNPs) is a substance secreted from the ventricles and lower chambers of the heart. BNPs are secreted in response to changes in pressure that occur when heart failure develops. Plasma BNP levels increase when symptoms of heart failure worsens, and decreases when the heart failure condition is healthy or stable (Gotzmann et al., 2014). Blood samples were collected in EDTA-containing tubes from the 44 subjects. The EDTA is an anticoagulant, inhibiting thrombosis. The collected blood samples were then put through centrifugation. The plasma BNP levels were measured prior to the TAVI procedure, as well as 30 days after using a chemoluminescent immunoassay kit (Gotzmann et al., 2014). The baseline levels of plasma BNP were 725±837 pg/ml (Gotzmann et al., 2014). 30 days after TAVI, the plasma BNP levels significantly reduced to 423-±320 pg/ml, indicating a reduction of neurohormonal activation (Gotzmann et al., 2014).

In conclusion, the preliminary results show a significant clinical benefit and a reduction of neurohormonal activation in patients with severe and symptomatic aortic valve stenosis early after TAVI. The main finding of this study is that TAVI leads to a rapid reduction of neurohormonal activity, an improvement of quality of life and a significantly enhanced functional capacity (Gotzmann et al., 2014).

Measurement of B-type Natriuretic Peptide Levels used to assess neurohormonal activation in patients after TAVI procedure

Sourced from Gotzmann et al., 2014

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