Current Catheter Intervention for Various Cardiovascular Diseases

Catheter intervention is constantly evolving and has developed with increasing patient needs because it is less invasive than cardiovascular surgery. Catheter intervention can be used for various fields such as coronary artery disease (CAD), peripheral arterial disease (PAD), and structural heart disease (SHD) through the development of a variety of devices and techniques for each specific disease. Thus, catheter intervention has become the first choice in many fields because of its proven efficacy and safety. Although every patient may not be suitable, catheter-based treatment should be chosen for the best strategy based on the medical condition of the individual patient and their long-term prognosis.


Introduction
Grüntzig successfully performed coronary balloon angioplasty first in humans in 1977 in Zurich, Switzerland. By about 1990, patients with CAD were more commonly treated by angioplasty than by coronary artery bypass surgery. This treatment approach is now referred to as plain old balloon angioplasty (POBA). Since the late 1990s, most balloon angioplasties have been replaced by stenting. Although stent implantation improved immediate and long-term patency, it created the new condition in-stent restenosis (ISR), which was observed in about 20-30% of patients after stent implantation. Drug-eluting stents (DES) were developed as a new stent technology and they succeeded in reducing ISR and re-intervention. On the other hand, the number of patients with PAD also increased with the aging of the population and due to increases in risk factors of atherosclerosis such as diabetes, smoking, dyslipidemia, hyperten-sion, and metabolic syndrome. Recently, many diagnostic tools such as ankle brachial index (ABI), skin perfusion pressure (SPP), duplex ultrasound, MRA, and 3-D CTA, as well as and therapeutic devices and procedural techniques like endovascular therapy (EVT) have been used in PAD, which improved the procedural results and patient outcome. Moreover, recently the target disease of catheter intervention has shifted to SHD since establishment of the efficacy of intervention in atherosclerotic disease. In this manuscript, we report on the current status of intervention technology, including Amplatzer Septal Occluder (ASO) and Transcatheter Aortic Valve Implantation (TAVI).

Current status of coronary intervention
DES have been available since 2004 and drug coating balloons (DCB) since 2014 in Japan. These devices markedly reduced ISR, the Achillesʼ heel of PCI 1)-4) . 197 Health Topics for Tokyoites However, the first generation DES had problems, the risk of both late stent thrombosis (LST) and very late stent thrombosis (VLST), which were associated with the discontinuation of dual antiplatelet therapy (DAPT) 5) 6) . These kinds of thromboses were interpreted to be related to the inflammatory response of polymer based reaction vulnerable plaque rupture of neo-atherosclerosis, mal-apposition of the stent strut, and impaired neo-intimal coverage in the stent site 7)-9) . urrent stent technology enables the use of 2 nd and 3 rd generation DES. These DES cause less polymer reactions because they use a high bio-compatible polymer or bioresorbable polymer. Thus, LST and VLST became rare complications after PCI and these stents have been proven safer than bare metal stents (BMS) in patients with acute coronary syndrome (ACS) 10) 11) . Recently, we have been performing more than 500 cases of PCI a year with a lower ISR rate (ISR rate in 2015 was 7.7% in angiographic follow-up). Moreover, LST and VLST are also very rare complications at our hospital.
In recent clinical settings, chronic total occlusion (CTO) is frequently seen, and registry studies have reported an incidence up to 50% in patients with significant coronary artery disease undergoing coronary angiography 12) , and they account for about 10-15% of all percutaneous revascularizations 13) . Although the clinical significance of CTO remains variable and controversial, some clinical studies have demonstrated that PCI in CTO vessels improved clinical outcomes, such as improved left ventricular function, decreased left ventricular mass, and the provision of collateral vessels to other coronary beds for protection against future events. Recently, clinical studies and meta-analyses have suggested that successful PCI in CTO vessels was associated with improved long-term survival 14)-17) . Moreover, the procedural success rate has improved to about 80% due to advancements in equipment such as tapered-tipped guidewires, special micro-catheters for CTO, and also with new procedural techniques for CTO such as the parallel wire technique, sea-saw wire technique, and bidirectional approach with low risk complications 18) . Long-term patency in CTO vessels has also demonstrated DES (sirolimus-eluting stent) markedly reduced ISR by 12% and the target vessel revascularization rate by 17% in 5 years clinical follow-up (PRISON II) 19) . We also perform PCI in CTO vessels in about 20-30 cases a year with a high success rate. (Success rate in CTO in 2015 was approximately 95%).

Current status of endovascular therapy (EVT)
Atherosclerotic disease occurs in various arteries such as the carotid artery, subclavian artery, renal artery, abdominal artery, and the arteries leading to the lower limbs. These diseases are known as PAD. Different symptoms are observed depending on the site of the vessels involved. The Trans-Atlantic Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC I), which in the subsequent version was named the Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II), provided expert recommendations on the diagnosis and treatment of PAD in 2007 20) . This guideline aimed to provide guidance on treatment decisions relating to the optimal revascularization strategy (endovascular vs surgical) based on the anatomic and clinical status of the patient. Regarding current device technology in this field, immediate and long-term results have been markedly improved by new specific balloons and guidewires and also stents. In subclavian artery stenosis, some clinical trials have reported the efficacy and safety in subclavian artery stenting. However, these trials had very small numbers of patients in a single center experience and relatively short follow-up periods. Recently, our investigator group (SCALLOP investigators) reported an acceptable outcome in terms of perioperative complications and long-term patency (5-year primary patency was 80.3%) 21) . Most PAD occurs in the lower limbs. The advent of Nitinol self-expandable stents dramatically changed EVT in the lower limbs. Although it is recommended complex aorto-iliac lesions such as TASC C-D classifications undergo surgical revascularization in this guideline, EVT by primary stenting is a well established first choice treatment strategy in patients with aorto-iliac disease, regardless of the TASC classification (5-year primary patency and secondary patency were 77.5% and 98.5%, respectively) 22) . The femoro-popliteal and BK areas of EVT still do not have enough long-term results, even though limb salvage has produced adequate results in patients with critical limb ischemia. We have been performing more than 100 cases of EVT a year in patients with non-carotid artery stenosis PAD.

Atrial septal defect (ASD)
ASD is the most common congenital heart disease after a bicuspid aortic valve in adults. Symptomatic ASD leads to significant morbidity and mortality. An untreated ASD may result in right ventricular failure, atrial arrhythmias, paradoxical embolism, pulmonary hypertension, and cyanosis secondary to reversal of a shunt from pulmonary vascular disease. American Heart Association (AHA) guidelines recommend the closure of secundum ASDs, either surgically or percutaneously, in patients with right atrial heart volume overload 23) . Transcatheter closure of secundum ASDs has been demonstrated to be safe and effective in both children and adults, with a similar success rate and lower complication rate compared to surgery, and the potential for decreased hospital stay 24)-26) . This device can only be used by a certified operator in a certified hospital in Japan. A total of 65 hospitals can use this device (March 2016) in Japan, and we started treating ASD using this device in 2014.

1) Amplatzer septal occluder (ASO)
This is a self expandable device constructed from 0.004-0.008 inch braided nitinol wires with polyester fabric patches sewn securely into the device to increase occlusion properties. The ASO device consists of a continuous braided structure comprised of two retention disks, a right and left atrial retention disk, connected by a central waist that is either 3 or 4 mm in length. There are various sizes available, ranging from 4 mm to 38 mm ( Figure-1).
For implantation of this device using a percutaneous technique with fluoroscopic and echocardiographic image guidance, a standard 0.035 inch guidewire is inserted through the defect into the left atrium from the right atrium. The Amplatzer sizing balloon is then advanced over the guidewire into the defect to determine the diameter of the defect. The sizing balloon is used to measure the size of the defect with trans-esophageal echocardiography (TEE) using a stop flow technique with a Doppler ultrasound method. Following this, the sizing balloon is removed and a delivery sheath that matches the size of each individual ASO device is inserted. Thus, the ASO device is inserted through the delivery sheath to the distal tip of the catheter using a delivery cable that is attached to the device end screw. Utilizing fluoroscopic and echocardiographic assessment of the device placement, the delivery system is advanced into the left atrium. The distal disc of the device is then deployed and positioned up against the left side of the atrial septum. Next, the delivery system is retracted across the ASD and is positioned in the right atrium where the proximal disc is deployed within the right atrium. The physician confirms the two discs are positioned together on opposing sides of the ASD in the correct location. The device can be retracted and either repositioned or replaced prior to final release of the device from the delivery cable (Figure-2).
Secundum ASDs can vary greatly in size and shape, but do not directly involve the major cardiac structures (vena cava, right pulmonary veins, coronary sinus, or atrioventricular valves). Distances to these structures are important considerations for transcatheter closure since distances greater than 5 mm are needed. The defect tissue rims must be present and substantial enough to anchor the device (Figure-3).
However, a recent study demonstrated that only 46 of 190 patients (24.2%) were found to have centrally placed defects which were ideally suited for percutaneous closure by evaluation of morphological variations of secundum-type ASD. Defects with a deficient superior anterior rim were the most frequent morphological variation of secundum-type ASD in this study and were found in 80 of 190 patients (42.1%).
Thus, a deficiency of the atrial septal rim at any location without a superior anterior rim around the defect (inferior posterior, inferior anterior, superior posterior, posterior) was deemed to be unsuitable for percutaneous closure and therefore patients were referred for surgical closure 27) . Major complications of this procedure are very rare in Japan but include death (0 of 7,223 cases: 0%), device embolization (30 of 7,223 cases: 0.42%), and erosion (13 of 7,223 cases: 0.18%) (2005-2015).

2) Case of atrial septal defect
A 21 year-old man was referred from another clinic. He played baseball in high school and was on his university baseball team. ECG findings revealed no obvious right axis deviation or right bundle branch block. He had no particular past history or family history. However, chest x-rays showed mild cardiomegaly and bilateral PA dilatation. Trans- thoracic echocardiography (TTE) revealed a left to right atrial shunt with a Qp/Qs of 1.6 and right cardiac overload. TEE also identified a septal defect of approximately 14 mm in diameter and deficiency of the aortic rim was relatively wide at an angle of 0 to 60 degrees (Figure-4, 5). Although there was potential risk of device embolization and erosion after ASO device closure, he decided to undergo trans-catheter closure during university because this treatment is a minimally invasive therapy compared to surgical closure. Thus, he was admitted to our hospital for ASO device implantation.

3) Procedure
At first, we inserted a 4 Fr sheath from the right femoral artery and started continuous blood pressure monitoring. An anesthesiologist then started general anesthesia before TEE and continuously during the procedure. Next, we inserted two sheaths via the bilateral femoral veins and performed intracardiac echocardiography (ICE) from the left femoral sheath. (If the patient is not suitable for general anesthesia for any of a number of reasons, ICE guided ASO under local anesthesia is also a treatment option). From the right femoral sheath, a standard 0.035 inch guidewire is inserted

Figure-5 Schema of the present case
Atrial septal defect is deviated upwards, near the aortic root.

Figure-6
ICE: Intracardiac echocardiography TEE: Transesophageal echocardiography Allow: Device size determination using a stop flow technique using a sizing balloon through the defect into the left atrium from the right atrium. The guidewire is then changed to an Amplatzer super stiff 0.035 inch wire using a 5 Fr multipurpose catheter. A sizing balloon was inserted on this guidewire through the defect and inflated for measuring with a stop flow technique by Doppler ultrasound (Figure-6). In this case, stop flow could see 14 mm with inflation. Although TEE revealed a 14 mm diameter defect, we chose a 16 mm device because the wide range of the aortic rim deficiency has a high risk of device embolization due to dislodging of the device.
However, TEE after 16 mm device implantation should demonstrate some residual shunt flow through the device (Figure-7). Thus, we decided to retrieve this device and switch it to a device that was 2 mm larger. After increasing the size of the Figure-9 This image shows that the device is gently pulled by the delivery cable to confirm the device was firmly deployed to the atrial septum.  (Figure-8).
An ASO device was implanted in a good position through the defect and stop flow was verified by TEE and ICE, following which we performed a ʻMinnesota wiggleʼ to ensure that the device was firmly deployed within the atrial septum. This is done by gently pulling and pushing the delivery wire to check if dislodging the device has been avoided ( Figure-9). After "wiggling", the device was detached from the delivery cable by unscrewing in a counterclockwise direction (Figure-10).

Aortic stenosis (AS)
Aortic valve stenosis, which is progressive narrowing of the aortic valve opening, is the most commonly acquired valvular heart disorder in the elderly. AS causes obstruction of left ventricular blood outflow, which induces cardiac pressure overload leading to left ventricular hypertrophy and ultimately congestive heart failure. AS has a long latency period followed by rapid disease progression, with approximately 50 percent of patients dying within two years of developing symptoms such as angina (chest pain or chest oppression on effort), dyspnea (shortness of breath), syncope, or congestive heart failure. Despite advances in cardiac surgery and low mortality rates after surgical aortic valve replacement (SAVR), up to one-third of patients with symptomatic aortic stenosis are not considered for SAVR, often due to frailty or comorbidities 28) .

1) Transcatheter aortic valve implantation (TAVI)
TAVI is the current topic of catheter intervention technology. This device consists of a catheter based artificial aortic heart valve and accessories used to implant the valve without open-heart surgery. The valve is made of cow tissue attached to a balloon-expandable, cobalt-chromium frame for support (Figure-11A).
The SAPIEN XT is compressed and placed on a balloon catheter. It could be inserted through the femoral artery if the patient is suitable for a  trans-femoral approach with a sufficient femoraliliac access root diameter. If the femoral arteries are not suitable, the valve can also be inserted through other arteries, the apex of the heart, or through the aorta (Figure-12). The catheter is advanced through the blood vessels until it reaches the diseased aortic valve. The valve is then expanded by the balloon and it anchors to the diseased valve. The SAPIEN XT functions in the same way as a normal valve, helping the blood flow properly by opening and closing like a door to force the blood to flow in the correct direction.
Transcatheter aortic valve implantation (TAVI) enables treatment of aortic stenosis without open heart surgery in patients with severe degenerative symptomatic AS who are either high risk or contraindicated for open heart surgery. The results of the randomized controlled PARTNER1 trial, comparing TAVI to the best medical therapy, have shown substantial survival benefits after 5 years 29) . In patients with a high surgical risk, TAVI was not inferior to surgery after 5 years 30) (Figure-13).
In intermediate risk patients in the PARTNER 2 trial, the rate of death from any cause or disabling stroke was similar in the TAVR group and the surgery group (p = 0.001 for non-inferiority) at 2 years 31) . Moreover, TAVI resulted in a lower rate of death from any cause or disabling stroke in the trans-femoral-access cohort compared with the SAVR cohort (Figure-14).
The Edwards SAPIEN XT Trans-catheter Heart Valve (often referred to as the SAPIEN XT) has been available in Japan since October 2013. TAVI can only be performed at one of the 94 certified hospitals in Japan (March 2016). At our hospital, we started treating patients with high-risk severe AS using TAVI on February 18, 2016. Another device will become available for TAVI later in 2016.
The Core Valve is a multilevel self-expanding and fully radiopaque nitinol frame with a diamond cell configuration that holds a tri-leaflet porcine pericardial tissue valve and anchors the device in Figure-14 Time-to-Event curves for the primary composite end point Death from any cause or disabling stroke was similar in the TAVR group and the surgery group (76.3% were accessed by the trans-femoral route and 23.7% were via. trans-thoracic). In the trans-femoral-access cohort, TAVR resulted in a lower rate of death from any cause or disabling stroke than did surgery (hazard ratio in the intention-to-treat analysis, 0.79; 95% CI, 0.62 to 1.00; p = 0.05; hazard ratio in the as-treated analysis, 0.78; 95% CI, 0.61 to 0.99; p = 0.04). This device can be implanted in patients with little or no distance between the coronary ostia and the leaflets insertion.
In a comparison, Core Valve has a larger potential orifice area when implanted in a degenerative surgical bio-prosthesis because the leaflets of this valve are located supra annulus. However, placement of a new permanent pacemaker due to atrioventricular block after Core Valve implantation was reported to be 2-3 fold greater than balloonexpandable valve implantation 32) .

2) Case of aortic stenosis
This is an 88-year-old man who was referred for evaluation of recent dyspnea. He had a past history of diabetes with chronic kidney disease and also a history of PCI using drug eluting stents. Although the ECG findings revealed no left ventricular hypertrophy, TTE revealed severe aortic stenosis with an aortic flow velocity of 3.9 m/s (mean pressure gradient is 36 mmHg) and an aortic valve area (AVA) of approximately 0.5 mm 2 .
His right intracranial internal carotid artery was occluded and the left intracranial internal carotid artery had severe stenosis detected by MRA.
He was recently admitted to our hospital to treat congestive heart failure (worsened DOE with raised BNP level of 964 pg/ml). He was admitted to our hospital after medical treatment for TAVI.

3) Procedure
At first, the temporary pacing catheter was inserted into the right ventricle for rapid pacing. Next, a pigtail catheter was advanced to the ascending aorta and aortography was performed to determine the perpendicular view which is important for deciding the precise position for TAVI. After aortography, the guidewire was retrogradely crossed to the left ventricle (LV) through the aortic valve. Following this, another pigtail catheter was advanced to the LV and a simultaneous pressure study was performed between the LV and ascending aorta.
Following the pressure study, balloon aortic valvuloplasty was performed using a 23 mm balloon   during rapid pacing at 160 bpm before TAVI (Figure-15). Next, TAVI was performed using a 26 mm SAPIEN-XT with 1 ml under filling of nominal size during rapid pacing because the aortic valve area of our measurement was 418.4 mm 2 on the 3D-CT before TAVI (Figure-16). After valve implantation, aortography showed only a trivial para-valvular leak from the SAPIEN-XT valve (Figure-17). Finally, a simultaneous pressure study revealed no pressure gradient between the LV and ascending aorta (Figure-18).

Conclusion
Advances in many devices and procedures for various cardiovascular diseases have led to the development of minimally invasive therapy, especially for those with SHD. In the future, various new devices will be approved such as left atrial appendage (LAA) closure devices, percutaneous edge-to-edge repair of the mitral valve devices (mitral clip), and patent foramen ovale closure devices. These new devices will continue to provide the benefit of less invasive treatment in patients with cardiovascular disease.

Figure-18
The left panel shows an approximate 60 mmHg pressure gradient of the peak to peak between the left ventricle and aorta. The right panel shows almost no pressure gradient of the peak to peak.