Structural Heart Disease and Transcatheter Heart Valves

Aortic Valve Stenosis

The aortic valve is one of the 4 valves of the heart and it ensures blood flow from the heart to the rest of the body. The normal aortic valve opening is 3-4 cm². The stenosis of the valve is considered significant when the opening is reduced to less than 1 cm².

The degenerative mechanism that causes aortic valve stenosis (narrowing) is dynamic and evolving. The main features of this process are gradual stiffening and thickening of the valve with calcium deposits that progressively limit leaflet mobility and eventually narrow the valve. Approximately 5% of the elderly population (>75 years) have developed at least moderate aortic valve stenosis.

When the condition becomes severe, it develops rapidly and the prognosis is poor, with high morbidity and hassles for the patients and their families.

The most common symptoms of aortic valve stenosis are shortness of breath, angina and dizziness, up to syncopal attacks. After the onset of symptoms, average patient survival drops drastically.

Treatment

Pharmaceutical treatment can relieve some of the symptoms temporarily, but it does not affect or treat the valve condition. The only treatment is valve replacement, which could only be performed with open surgery until a few years ago. However, many patients are already of an advanced age when the symptoms appear and often suffer from other conditions that greatly increase the risk of conventional cardiac surgery, or even prohibit it. Therefore, surgical replacement is considered too risky in these patients and they often do not undergo surgery (it is estimated that 1 in every 2 patients who must undergo conventional surgical replacement of aortic valve is rejected). Prognosis in these patients is poor and morbidity long and painful.

Transcatheter Aortic Valve Replacement (Implantation): TAVR or TAVI is being successfully performed since 2007, initially on patients who could not have been treated in the past. Since 2011, TAVR has also been approved and is successfully performed on patients who could have undergone surgical replacement, but were considered high risk. With low single-digit mortality rates and fast recovery and return to daily activities, the benefits of this method are obvious.

In 2016, the results of the first clinical trials showed better survival with TAVR compared to the surgical replacement, even in lower (moderate) risk patients, and the use of the method has since been extended to these patients as well. In 2018, newer clinical trials produced similar results for the TAVR method in low-risk patients (essentially for all patients now). As a result, the method was recently (2019) approved and indicated by the FDA for application on essentially all patients with aortic valve stenosis.

Image 1. Illustration of implanted transcatheter valves in the position of the aortic valve

The Studies

The Transcatheter Aortic Valve Replacement is the most researched valve replacement method, as well as one of the most researched treatments in Cardiology and Cardiac Surgery in general.

The results of the randomized PARTNER-B study were announced in 2010, when it was found that the transcatheter method for treating aortic valve stenosis is changing the natural history of the disease and improves survival. Older patients with coexisting conditions, who would generally be treated conservatively due to the forbiddingly high surgical risk, underwent randomized transfemoral valve implantation and showed remarkable improvement of symptoms, reduced need for hospitalization by 54% and reduced morbidity by 45% as early as the first year. Consequently, the method was recognized for this patient population, who would otherwise be doomed to severe morbidity and very poor prognosis. It is estimated that there are at least 1,000 such patients in Greece (per year) who could benefit from the transcatheter approach.

The results of the randomized PARTNER-A study were announced in March 2011. PARTNER-A is significant in that it randomized high-risk patients (Logistic Euroscore ≥ 15%), who, however, were not rejected for surgical treatment. 30-day morbidity for the transcatheter procedure (3.4%) was almost 50% lower compared to the corresponding surgical replacement (6.7%), proving that they are at least equivalent treatments. Survival in the first year was 2.6% higher for the transcatheter method. Especially with regard to the transfemoral implantation, 30-day survival was significantly higher compared to the surgical replacement.

The results of PARTNER-A provided the first comparative assessment of the transcatheter implantation compared to the surgical replacement of the aortic valve, demonstrating that even high-risk patients who can undergo surgery enjoy just as good results with transcatheter implantation, and with all the benefits of a less invasive method. This population is estimated at around 25% of patients who undergo surgical replacement to date (patients with a Logistic Euroscore ≥ 15%) (approximately 300 patients/year in Greece, on top of the ~1000 deemed inoperable).

The first randomized clinical study that proved the superiority of the transcatheter method over the conventional surgical replacement was announced in the spring of 2014 (CoreValve US Pivotal High Risk Study). In this study, 795 high-risk patients (Logistic Euroscore average of 18%) who were eligible for conventional surgery were randomized to transcatheter or surgical replacement. The morbidity of those who underwent the transfemoral method was significantly lower both at 1 month (3.3% for the transcatheter, 4.5% for the surgical) and at 1 year (14.2% for the transcatheter, 19.1% for the surgical).

The results of the latest generation SAPIEN 3 valve by Edwards Lifesciences on 1,655 high and medium surgical risk patients were announced in the beginning of 2016. This study showed the lowest 30-day morbidity rates to date, i.e. 1.6% for the transfemoral procedure in high-risk patients and 1.1% in medium-risk patients.

The results of the PARTNER 2 study, which randomized 2,032 medium-risk patients (STS score 4%-8%) to transcatheter or surgical aortic valve replacement, were also announced in the beginning of 2016. The patients who underwent transfemoral valve implantation had better early survival as opposed to those who underwent conventional surgical replacement. The results of these studies provided the indication and established the transcatheter replacement in medium-risk patients (around 25% of patients undergoing surgical replacement up until that time).

The results of the PARTNER 3 and the EVOLUT Low Risk Trials were both announced at the beginning of 2019. They included 2,468 low-risk patients (STS < 4%) and during the 2-year follow-up, they showed that not only is TAVR safe and effective in these patients as well, but the incidence of death or stroke was halved compared to the conventional surgical replacement (PARTNER 3 and EVOLUT Low Risk Trials combined: 2.6% vs. 5.2%). In practical terms this means that if 200 such patients undergo TAVR as opposed to conventional surgery, 5 more will return for the 2-year follow-up alive and without having suffered a stroke. These are concrete results and will unavoidably lead to the generalized application of the TAVR in patients with aortic valve stenosis.

As of 2007, there has been wide clinical acceptance of the method (initially in Europe, followed by the USA and Japan) and the number of procedures performed followed a geometric progression, with an 40%-80% rise annually. More than 700,000 implantations have been performed to date (09/2019) globally (3,500 in Greece). In many countries, transcatheter implantations have surpassed the surgical ones. In most western European countries, more than 100 (and up to 300) transcatheter implantations are performed per 1 million population.

With regard to the clinical results in everyday practice, the announcements from the most recent register recordings and the studies show that 30-day morbidity in high/medium-risk patients who undergo transfemoral transcatheter replacement is around 2%-4%, while it is 1% in low-risk patients. The recorded 30-day morbidities for transthoracic and transaortic implantations are around 3%-8%.

Transcatheter implantations of all valve types currently available (SAPIEN 3, Edwards Lifesciences; Evolut PRO, Medtronic; Portico, Abbott; ACURATE neo and LOTUS Edge, Boston Scientific) are performed at HYGEIA Hospital, using all possible implantation methods (transfemoral, transaortic, transthoracic, subclavian route etc.). The Department staff’s experience exceeds 1,400 procedures, while 30-day morbidity of transfemoral procedures has been < 2%.

Image 2: The SAPIEN 3 (Edwards Lifesciences), Evolut PRO (Medtronic), Portico (Abbott), ACURATE neo and LOTUS Edge (Boston Scientific) transcatheter valves (from top left to bottom right)

Transcatheter Heart Valve Resilience

There is plenty of detailed follow-up information on many patients who carry transcatheter valves in the last 10 years and there have been no concerns as to their long-term resilience and functionality. Besides, they are manufactured by the same companies that manufacture surgical valves and undergo the same rigorous bench testing. It is expected that they will continue to operate well for just as long (i.e. 12-16 years). However, even if they malfunction, this will happen gradually and it will be possible to replace them with new transcatheter valves that will be implanted in the same simple manner. This is already being done on patients with malfunction of older surgically placed bioprosthetic valves, however, this time these patients are treated with the transcatheter method rather than undergoing a new surgical procedure.

Aortic Valve Regurgitation

Although it is rarer than aortic valve stenosis, aortic valve regurgitation causes the same serious problems and treatment is once again replacement of the faulty valve. Provided it can be performed, transcatheter replacement is the best choice for high-risk patients.

The Procedure

Transfemoral procedure

The procedure is performed through the femoral artery, similarly to a coronary angiography. Strict antisepsis measures are in place in the HYGEIA Hospital Hybrid Operating Room, where the procedure is performed. General anesthesia and intubation are not required, but patients are placed under sedation, so that they remain calm and can cooperate. The procedure usually lasts less than 30 minutes, but patients remain in the operating room for about 90 minutes total (preparation upon arrival and departure). The entry point of the valve into the femoral artery is sealed externally, while there is no incision on the skin.

Patients remain on bed rest for the first night postoperatively, at the Intensive Care Unit or High Dependency Unit, and then they are fully mobile and remain hospitalized in a simple ward for another 1-3 days. In the vast majority of patients (> 95%), the femoral arteries are suitable for valve implantation. It is generally accepted that transfemoral implantations are preferable, as they are less invasive and carry a lower risk.

Transaortic and transapical (transthoracic) procedure

Following the advancement and improvement of transcatheter valves, transaortic and transapical implantations are rarely performed these days (less than 5% of patients), and only when the femoral arteries are deemed unsuitable for transfemoral implantation (due to small size, stenosis, etc.). The procedure is performed under general anesthesia and the valve is implanted either through the aorta (transaortic), through a small incision between the ribs at the top of the chest, or directly through the heart (transapical), through a small incision between the ribs on the left, under the nipple. The procedure usually lasts less than 1 hour, but patients remain in the operating room for about 2 hours total (preparation upon arrival and departure). The incision on the skin between the ribs is around 3-5 cm long and is sutured closed. Patients remain on bed rest in the Intensive Care Unit for the first day postoperatively and then they are hospitalized in a simple ward for another 2-3 days.

These patients also enjoy the key benefits of the method, avoiding a sternotomy and extracorporeal circulation. The SAPIEN 3 and ACURATE neo valves may be implanted transaortically and transapically, the Evolut R and Portico transaortically, and the JenaValve transapically.

Eligibility testing

A patient’s eligibility is assessed through a series of tests as an outpatient, and rarely is 1-day hospitalization required. The tests include coronary angiography to check the heart arteries (invasive or bloodless with CT), cardiac CT, CT angiography of the limbs to determine their suitability for valve insertion, echocardiography, blood tests and any other exams deemed necessary, depending on each patient. Patients are also evaluated by the entire medical team that will participate in the procedure (cardiologists, cardiac surgeons, anesthesiologists, vascular surgeons, etc., i.e. the Heart Team). After testing, they decide on: the implantation method (transfemoral, transaortic, transapical, etc.), most suitable valve type (for anatomical and other reasons, one type of valve is often preferable to another in each patient) and suitable valve size.

Through this procedure, it is also possible to manage any significant stenoses encountered in the coronary arteries using angioplasty and stents. Finally, palliative valvuloplasty (valve opening with balloon) may be performed on gravely ill patients, so they may undergo valve implantation at a later date.

Mitral Valve Regurgitation

It is the most frequent valve disease and it is estimated that 8%-10% of people aged over 75 may develop at least moderate mitral valve regurgitation. The inability of this valve to close tightly results in part of the blood, which was to be channeled to the entire body through the aorta, flowing back into the lungs.

Severe mitral valve regurgitation causes heart failure symptoms (fatigue and shortness of breath during natural fatigue, up to acute pulmonary edema) and predisposition for developing atrial fibrillation (arrhythmia) and stroke.

Mitral valve regurgitation is distinguished into functional (usually due to coronary disease or dilated cardiomyopathy) and organic (often degenerative, which causes leaflet prolapse). Pharmaceutical treatment may manage and temporarily improve some of the symptoms caused by severe mitral valve regurgitation. However, given that the problem is primarily mechanical, it cannot treat it.

Surgical treatment of the functional regurgitation of the mitral valve is attempted only when the patient also suffers from coronary disease and must undergo aortocoronary bypass surgery for precisely this reason. Otherwise the benefit is unconfirmed and the risk of the procedure high. This is also the reason why patients rarely undergo surgical procedure just to treat the valve regurgitation. Transcatheter repair is applicable to them.

Surgical treatment of organic valve regurgitation usually involves open or endoscopic surgical repair. However, at times, this is not possible, in which case, it is replaced by a prosthetic valve. Nevertheless, there are many such patients who do not eventually undergo surgical treatment because they are deemed high risk for various reasons. Transcatheter repair is applicable to them.

MitraClip: Transcatheter mitral valve regurgitation repair system

The MitraClip system (Abbott Vascular) is based on the transcatheter placement of one or more clips in the mitral valve and aims to reduce or even eliminate the regurgitation. This minimally invasive mitral valve repair mimics the open surgery method by creating a double orifice (Alfieri method) and increases the treatment choices available to patients who suffer from severe valve regurgitation.

The MitraClip device places a clip in the mitral valve, without opening the patient’s chest and without incisions. The guide catheter is introduced through the femoral vein to reach the heart, similarly to a coronary angiography. The procedure is performed under general anesthesia, without using a heart-lung machine (extracorporeal circulation) and without a sternotomy. Hospitalization is two to three days postoperatively.

It has been proven to reduce the symptoms of heart failure and improve the quality of life in select patients with mitral valve regurgitation, similarly to the surgical method, but much safer. There is strong evidence available currently suggesting that it increases survival compared to conservative pharmaceutical treatment.

The system consists of three main subsystems:

• A steerable guide catheter
• A clip delivery system
• A MitraClip device (implant)

Image 1. The MitraClip system

The MitraClip is the first transcatheter mitral valve regurgitation repair system to receive the European CE certification in 2008 and be approved by the FDA in 2013, while more than 80,000 procedures have been performed globally to date.

The COAPT clinical trial, announced in 2018, included 603 patients with functional mitral valve regurgitation and compared the MitraClip with the conservative conventional treatment. It is extremely important that treatment using the MitraClip method showed significant and major reduction in morbidity, resulting in the US FDA extending the treatment indications in 2019.

In Greece, these procedures were performed for the first time by the HYGEIA Hospital Transcatheter Heart Valve Department in October 2011 and were met with great success. The program has been successfully continuing since then and more than 250 clips have been implanted.

The clinical application of the transcatheter mitral valve regurgitation repair using the PASCAL system by Edwards Lifesciences was approved in February 2019.

The HYGEIA Hospital Transcatheter Heart Valve Department was among the main investigators of the CLASP trial, which led to the PASCAL system receiving the CE mark due to its excellent results. The PASCAL system is currently used for the transcatheter repair of the mitral valve. The technique is similar to the one used for the MitraClip system, which is being successfully applied at HYGEIA for many years. The first commercial application in Greece was at the HYGEIA Hospital Transcatheter Heart Valve Department in 2019.

Image 2. The PASCAL system

Possible treatment indications for MitraClip/PASCAL

The implantation of the clip may significantly reduce or even eliminate mitral valve regurgitation in the following cases:

• Significant functional mitral valve regurgitation that does not require surgical treatment of coexisting coronary artery disease.
• Significant organic mitral valve regurgitation in high surgical risk patients.

The anatomical eligibility criteria are examined using transthoracic and intraesophageal echocardiography (Doppler ultrasound).

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• Wilczek K, Chodór P, Przybylski R, Krasoń M, Niklewski T, Nadziakiewicz P, Głowacki J, Kusa J, Goddyn D, Spargias K, Zembala M. First in Poland transcatheter, transfemoral aortic valve implantation in elderly symptomatic high-risk patient with aortic stenosis-novel Zabrze experience. Kardiol Pol 2009;67:219-23.
• Kolettis TN, Spargias K, Stavridis GT. Combined transapical aortic valve implantation with coronary artery bypass grafting in a young patient with porcelain aorta. Hellenic J Cardiol 2009;50:79-82.
• Trendafilova D , Jorgova J, Simeonov P. Acknowledgement to Dr K Spargias. First Transfemoral Aortic Valve Implantation In Bulgaria. The Internet Journal of Cardiology 2010;9:2.

Aortic Valve Stenosis

The aortic valve is one of the 4 valves of the heart and it ensures blood flow from the heart to the rest of the body. The normal aortic valve opening is 3-4 cm². The stenosis of the valve is considered significant when the opening is reduced to less than 1 cm².

The degenerative mechanism that causes aortic valve stenosis (narrowing) is dynamic and evolving. The main features of this process are gradual stiffening and thickening of the valve with calcium deposits that progressively limit leaflet mobility and eventually narrow the valve. Approximately 5% of the elderly population (>75 years) have developed at least moderate aortic valve stenosis.

When the condition becomes severe, it develops rapidly and the prognosis is poor, with high morbidity and hassles for the patients and their families.

The most common symptoms of aortic valve stenosis are shortness of breath, angina and dizziness, up to syncopal attacks. After the onset of symptoms, average patient survival drops drastically.

Treatment

Pharmaceutical treatment can relieve some of the symptoms temporarily, but it does not affect or treat the valve condition. The only treatment is valve replacement, which could only be performed with open surgery until a few years ago. However, many patients are already of an advanced age when the symptoms appear and often suffer from other conditions that greatly increase the risk of conventional cardiac surgery, or even prohibit it. Therefore, surgical replacement is considered too risky in these patients and they often do not undergo surgery (it is estimated that 1 in every 2 patients who must undergo conventional surgical replacement of aortic valve is rejected). Prognosis in these patients is poor and morbidity long and painful.

Transcatheter Aortic Valve Replacement (Implantation): TAVR or TAVI is being successfully performed since 2007, initially on patients who could not have been treated in the past. Since 2011, TAVR has also been approved and is successfully performed on patients who could have undergone surgical replacement, but were considered high risk. With low single-digit mortality rates and fast recovery and return to daily activities, the benefits of this method are obvious.

In 2016, the results of the first clinical trials showed better survival with TAVR compared to the surgical replacement, even in lower (moderate) risk patients, and the use of the method has since been extended to these patients as well. In 2018, newer clinical trials produced similar results for the TAVR method in low-risk patients (essentially for all patients now). As a result, the method was recently (2019) approved and indicated by the FDA for application on essentially all patients with aortic valve stenosis.

Image 1. Illustration of implanted transcatheter valves in the position of the aortic valve

The Studies

The Transcatheter Aortic Valve Replacement is the most researched valve replacement method, as well as one of the most researched treatments in Cardiology and Cardiac Surgery in general.

The results of the randomized PARTNER-B study were announced in 2010, when it was found that the transcatheter method for treating aortic valve stenosis is changing the natural history of the disease and improves survival. Older patients with coexisting conditions, who would generally be treated conservatively due to the forbiddingly high surgical risk, underwent randomized transfemoral valve implantation and showed remarkable improvement of symptoms, reduced need for hospitalization by 54% and reduced morbidity by 45% as early as the first year. Consequently, the method was recognized for this patient population, who would otherwise be doomed to severe morbidity and very poor prognosis. It is estimated that there are at least 1,000 such patients in Greece (per year) who could benefit from the transcatheter approach.

The results of the randomized PARTNER-A study were announced in March 2011. PARTNER-A is significant in that it randomized high-risk patients (Logistic Euroscore ≥ 15%), who, however, were not rejected for surgical treatment. 30-day morbidity for the transcatheter procedure (3.4%) was almost 50% lower compared to the corresponding surgical replacement (6.7%), proving that they are at least equivalent treatments. Survival in the first year was 2.6% higher for the transcatheter method. Especially with regard to the transfemoral implantation, 30-day survival was significantly higher compared to the surgical replacement.

The results of PARTNER-A provided the first comparative assessment of the transcatheter implantation compared to the surgical replacement of the aortic valve, demonstrating that even high-risk patients who can undergo surgery enjoy just as good results with transcatheter implantation, and with all the benefits of a less invasive method. This population is estimated at around 25% of patients who undergo surgical replacement to date (patients with a Logistic Euroscore ≥ 15%) (approximately 300 patients/year in Greece, on top of the ~1000 deemed inoperable).

The first randomized clinical study that proved the superiority of the transcatheter method over the conventional surgical replacement was announced in the spring of 2014 (CoreValve US Pivotal High Risk Study). In this study, 795 high-risk patients (Logistic Euroscore average of 18%) who were eligible for conventional surgery were randomized to transcatheter or surgical replacement. The morbidity of those who underwent the transfemoral method was significantly lower both at 1 month (3.3% for the transcatheter, 4.5% for the surgical) and at 1 year (14.2% for the transcatheter, 19.1% for the surgical).

The results of the latest generation SAPIEN 3 valve by Edwards Lifesciences on 1,655 high and medium surgical risk patients were announced in the beginning of 2016. This study showed the lowest 30-day morbidity rates to date, i.e. 1.6% for the transfemoral procedure in high-risk patients and 1.1% in medium-risk patients.

The results of the PARTNER 2 study, which randomized 2,032 medium-risk patients (STS score 4%-8%) to transcatheter or surgical aortic valve replacement, were also announced in the beginning of 2016. The patients who underwent transfemoral valve implantation had better early survival as opposed to those who underwent conventional surgical replacement. The results of these studies provided the indication and established the transcatheter replacement in medium-risk patients (around 25% of patients undergoing surgical replacement up until that time).

The results of the PARTNER 3 and the EVOLUT Low Risk Trials were both announced at the beginning of 2019. They included 2,468 low-risk patients (STS < 4%) and during the 2-year follow-up, they showed that not only is TAVR safe and effective in these patients as well, but the incidence of death or stroke was halved compared to the conventional surgical replacement (PARTNER 3 and EVOLUT Low Risk Trials combined: 2.6% vs. 5.2%). In practical terms this means that if 200 such patients undergo TAVR as opposed to conventional surgery, 5 more will return for the 2-year follow-up alive and without having suffered a stroke. These are concrete results and will unavoidably lead to the generalized application of the TAVR in patients with aortic valve stenosis.

As of 2007, there has been wide clinical acceptance of the method (initially in Europe, followed by the USA and Japan) and the number of procedures performed followed a geometric progression, with an 40%-80% rise annually. More than 700,000 implantations have been performed to date (09/2019) globally (3,500 in Greece). In many countries, transcatheter implantations have surpassed the surgical ones. In most western European countries, more than 100 (and up to 300) transcatheter implantations are performed per 1 million population.

With regard to the clinical results in everyday practice, the announcements from the most recent register recordings and the studies show that 30-day morbidity in high/medium-risk patients who undergo transfemoral transcatheter replacement is around 2%-4%, while it is 1% in low-risk patients. The recorded 30-day morbidities for transthoracic and transaortic implantations are around 3%-8%.

Transcatheter implantations of all valve types currently available (SAPIEN 3, Edwards Lifesciences; Evolut PRO, Medtronic; Portico, Abbott; ACURATE neo and LOTUS Edge, Boston Scientific) are performed at HYGEIA Hospital, using all possible implantation methods (transfemoral, transaortic, transthoracic, subclavian route etc.). The Department staff’s experience exceeds 1,400 procedures, while 30-day morbidity of transfemoral procedures has been < 2%.

Image 2: The SAPIEN 3 (Edwards Lifesciences), Evolut PRO (Medtronic), Portico (Abbott), ACURATE neo and LOTUS Edge (Boston Scientific) transcatheter valves (from top left to bottom right)

Transcatheter Heart Valve Resilience

There is plenty of detailed follow-up information on many patients who carry transcatheter valves in the last 10 years and there have been no concerns as to their long-term resilience and functionality. Besides, they are manufactured by the same companies that manufacture surgical valves and undergo the same rigorous bench testing. It is expected that they will continue to operate well for just as long (i.e. 12-16 years). However, even if they malfunction, this will happen gradually and it will be possible to replace them with new transcatheter valves that will be implanted in the same simple manner. This is already being done on patients with malfunction of older surgically placed bioprosthetic valves, however, this time these patients are treated with the transcatheter method rather than undergoing a new surgical procedure.

Aortic Valve Regurgitation

Although it is rarer than aortic valve stenosis, aortic valve regurgitation causes the same serious problems and treatment is once again replacement of the faulty valve. Provided it can be performed, transcatheter replacement is the best choice for high-risk patients.

The Procedure

Transfemoral procedure

The procedure is performed through the femoral artery, similarly to a coronary angiography. Strict antisepsis measures are in place in the HYGEIA Hospital Hybrid Operating Room, where the procedure is performed. General anesthesia and intubation are not required, but patients are placed under sedation, so that they remain calm and can cooperate. The procedure usually lasts less than 30 minutes, but patients remain in the operating room for about 90 minutes total (preparation upon arrival and departure). The entry point of the valve into the femoral artery is sealed externally, while there is no incision on the skin.

Patients remain on bed rest for the first night postoperatively, at the Intensive Care Unit or High Dependency Unit, and then they are fully mobile and remain hospitalized in a simple ward for another 1-3 days. In the vast majority of patients (> 95%), the femoral arteries are suitable for valve implantation. It is generally accepted that transfemoral implantations are preferable, as they are less invasive and carry a lower risk.

Transaortic and transapical (transthoracic) procedure

Following the advancement and improvement of transcatheter valves, transaortic and transapical implantations are rarely performed these days (less than 5% of patients), and only when the femoral arteries are deemed unsuitable for transfemoral implantation (due to small size, stenosis, etc.). The procedure is performed under general anesthesia and the valve is implanted either through the aorta (transaortic), through a small incision between the ribs at the top of the chest, or directly through the heart (transapical), through a small incision between the ribs on the left, under the nipple. The procedure usually lasts less than 1 hour, but patients remain in the operating room for about 2 hours total (preparation upon arrival and departure). The incision on the skin between the ribs is around 3-5 cm long and is sutured closed. Patients remain on bed rest in the Intensive Care Unit for the first day postoperatively and then they are hospitalized in a simple ward for another 2-3 days.

These patients also enjoy the key benefits of the method, avoiding a sternotomy and extracorporeal circulation. The SAPIEN 3 and ACURATE neo valves may be implanted transaortically and transapically, the Evolut R and Portico transaortically, and the JenaValve transapically.

Eligibility testing

A patient’s eligibility is assessed through a series of tests as an outpatient, and rarely is 1-day hospitalization required. The tests include coronary angiography to check the heart arteries (invasive or bloodless with CT), cardiac CT, CT angiography of the limbs to determine their suitability for valve insertion, echocardiography, blood tests and any other exams deemed necessary, depending on each patient. Patients are also evaluated by the entire medical team that will participate in the procedure (cardiologists, cardiac surgeons, anesthesiologists, vascular surgeons, etc., i.e. the Heart Team). After testing, they decide on: the implantation method (transfemoral, transaortic, transapical, etc.), most suitable valve type (for anatomical and other reasons, one type of valve is often preferable to another in each patient) and suitable valve size.

Through this procedure, it is also possible to manage any significant stenoses encountered in the coronary arteries using angioplasty and stents. Finally, palliative valvuloplasty (valve opening with balloon) may be performed on gravely ill patients, so they may undergo valve implantation at a later date.

Mitral Valve Regurgitation

It is the most frequent valve disease and it is estimated that 8%-10% of people aged over 75 may develop at least moderate mitral valve regurgitation. The inability of this valve to close tightly results in part of the blood, which was to be channeled to the entire body through the aorta, flowing back into the lungs.

Severe mitral valve regurgitation causes heart failure symptoms (fatigue and shortness of breath during natural fatigue, up to acute pulmonary edema) and predisposition for developing atrial fibrillation (arrhythmia) and stroke.

Mitral valve regurgitation is distinguished into functional (usually due to coronary disease or dilated cardiomyopathy) and organic (often degenerative, which causes leaflet prolapse). Pharmaceutical treatment may manage and temporarily improve some of the symptoms caused by severe mitral valve regurgitation. However, given that the problem is primarily mechanical, it cannot treat it.

Surgical treatment of the functional regurgitation of the mitral valve is attempted only when the patient also suffers from coronary disease and must undergo aortocoronary bypass surgery for precisely this reason. Otherwise the benefit is unconfirmed and the risk of the procedure high. This is also the reason why patients rarely undergo surgical procedure just to treat the valve regurgitation. Transcatheter repair is applicable to them.

Surgical treatment of organic valve regurgitation usually involves open or endoscopic surgical repair. However, at times, this is not possible, in which case, it is replaced by a prosthetic valve. Nevertheless, there are many such patients who do not eventually undergo surgical treatment because they are deemed high risk for various reasons. Transcatheter repair is applicable to them.

MitraClip: Transcatheter mitral valve regurgitation repair system

The MitraClip system (Abbott Vascular) is based on the transcatheter placement of one or more clips in the mitral valve and aims to reduce or even eliminate the regurgitation. This minimally invasive mitral valve repair mimics the open surgery method by creating a double orifice (Alfieri method) and increases the treatment choices available to patients who suffer from severe valve regurgitation.

The MitraClip device places a clip in the mitral valve, without opening the patient’s chest and without incisions. The guide catheter is introduced through the femoral vein to reach the heart, similarly to a coronary angiography. The procedure is performed under general anesthesia, without using a heart-lung machine (extracorporeal circulation) and without a sternotomy. Hospitalization is two to three days postoperatively.

It has been proven to reduce the symptoms of heart failure and improve the quality of life in select patients with mitral valve regurgitation, similarly to the surgical method, but much safer. There is strong evidence available currently suggesting that it increases survival compared to conservative pharmaceutical treatment.

The system consists of three main subsystems:

• A steerable guide catheter
• A clip delivery system
• A MitraClip device (implant)

Image 1. The MitraClip system

The MitraClip is the first transcatheter mitral valve regurgitation repair system to receive the European CE certification in 2008 and be approved by the FDA in 2013, while more than 80,000 procedures have been performed globally to date.

The COAPT clinical trial, announced in 2018, included 603 patients with functional mitral valve regurgitation and compared the MitraClip with the conservative conventional treatment. It is extremely important that treatment using the MitraClip method showed significant and major reduction in morbidity, resulting in the US FDA extending the treatment indications in 2019.

In Greece, these procedures were performed for the first time by the HYGEIA Hospital Transcatheter Heart Valve Department in October 2011 and were met with great success. The program has been successfully continuing since then and more than 250 clips have been implanted.

The clinical application of the transcatheter mitral valve regurgitation repair using the PASCAL system by Edwards Lifesciences was approved in February 2019.

The HYGEIA Hospital Transcatheter Heart Valve Department was among the main investigators of the CLASP trial, which led to the PASCAL system receiving the CE mark due to its excellent results. The PASCAL system is currently used for the transcatheter repair of the mitral valve. The technique is similar to the one used for the MitraClip system, which is being successfully applied at HYGEIA for many years. The first commercial application in Greece was at the HYGEIA Hospital Transcatheter Heart Valve Department in 2019.

Image 2. The PASCAL system

Possible treatment indications for MitraClip/PASCAL

The implantation of the clip may significantly reduce or even eliminate mitral valve regurgitation in the following cases:

• Significant functional mitral valve regurgitation that does not require surgical treatment of coexisting coronary artery disease.
• Significant organic mitral valve regurgitation in high surgical risk patients.

The anatomical eligibility criteria are examined using transthoracic and intraesophageal echocardiography (Doppler ultrasound).