Novel solutions applied in transseptal puncture

technique: a systematic review of current literature

Bibliographic Survey

Pedro André Gonçalves Morais, UP201400020

Doctoral Program in Biomedical Engineering

2014/2015

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Title: Novel solutions applied in transseptal puncture technique: a systematic review of

current literature

Abstract

Background: Access to the left atrium is required for several minimally invasive cardiac

interventions of the left heart. Hereto, transseptal puncture (TSP) technique was proposed,

which relies on the perforation of atrial septum through a catheter inserted in the right atrium

(RA) via the venous system under fluoroscopic guidance. Although this approach has been

used for many years, complications and procedural failures are common.

Purpose: Recently, a high number of authors proposed novel solutions to overcome the main-

limitations of TSP technique, increasing consequently the safety and feasibility of the

procedure. This study presents an overview of these novel methods, indicating their

advantages throughout the puncture procedure.

Material and Methods: A systematic review of literature was conducted through the analysis

of the articles published between 2008 and 2015. The search was performed in PubMed,

Scopus and ISI Web of Knowledge using the expression “transseptal puncture”. A total of 834

results were retrieved from database, and 192 results were selected for this review. Moreover,

these 192 results were divided into four categories, namely: 1) incidence studies; 2) intra-

procedural guidance techniques; 3) pre-procedural planning methods and 4) surgical

instruments.

Results: A total of 37 articles focused on incidence studies, presenting the number of TSP

interventions, puncture attempts, complications and failure rate. 24 articles suggested novel

intra-procedural guidance techniques. Pre-procedural planning strategies were proposed in a

total of 5 works. Regarding the surgical instruments, a total of 21 works were selected.

Conclusion: The novel 3D guidance techniques, surgical instruments and pre-intervention

planning approaches showed potential to overcome the main procedural

limitations/complications, through the reduction of the intervention time, radiation, number

of failures and complications.

Keywords: transseptal puncture, left atrium access, systematic review, optimal puncture

position

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1. Introduction

Percutaneous access of the left atrium (LA) is required in a large number of minimally

invasive procedures, such as catheter ablation for atrial fibrillation, paravalvular leakage repair,

percutaneous mitral valve replacement, pulmonary vein isolation and left atrial appendage

closure [1, 2]. These procedures show a high application rate (see Table 1) being a preferred

technique to the traditional open-chest surgery, due to the lower costs and lower complication

rate. However, the procedures are not free of risks being dependent of physician experience

and medical devices used (e.g. image acquisition or surgical equipment) [3]

Direct access to the LA is not physical possible, making these transcatheter procedures

cumbersome. Two techniques are commonly used to perform this task: transaortic (TA) access

and transseptal puncture (TSP). In TA access, a catheter inserted in the femoral artery is

retrogradely advanced through the aortic valve towards the left ventricle (LV). Subsequently,

the catheter is rotated 180° and advanced throughout the mitral valve (MV) into the LA

chamber. Regarding the TSP, a catheter is inserted into the right-atrium (RA) via the venous

system, through which a needle can be moved forward, in order to puncture the interatrial

septum (IAS) and consequently access the LA. Thus, TSP technique establishes a “more direct”

access route, when compared with TA approach. Nonetheless, in complex situations TSP

technique can perforate a large vessel (e.g. aorta) resulting in serious complications for the

patient.

Despite the similar performance and safety between the two techniques [3, 4], TA route

requires a 180° rotation of the catheter, complicating its manipulation and consequently

hampering the procedure. Moreover, the TA strategy uses an access route through the high-

pressure arterial system. Contrarily, TSP enters into the LA using the low-pressure venous

system. As such, in the last years a superior number of procedures based on TSP were

registered [3].

Furthermore, new strategies have been proposed to overcome the main-complications of

the TSP, through the inclusion of novel guidance, planning methods and surgical instruments

on the traditional procedure. In the current study we intend to present an overview of the new

strategies and summarize their advantages. Moreover, this study also presents a review of

clinical studies that reported incidence of TSP procedure.

As a summary, the current work introduces four novelties, namely: 1) an incidence study

about TSP approach; 2) a review of the recent guidance methods applied in TSP procedure; 3)

a review of recent intra-procedural planning methods for safe puncture zone recognition; and

4) an overview of novel surgical instruments recently used to puncture the IAS wall.

As a final remark, the current article is divided on six-main sections: 1) considerations

about atrial anatomy; 2) description of the traditional TSP method; 3) method used to identify

the relevant studies for this review; 4) aims and main-conclusion of the selected articles; 5)

discussion of the relevant articles, presenting their advantages and main drawbacks; and 6)

conclusions of the proposed review.

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Table 1 – Application rate of different percutaneous procedures that require TSP technique.

Procedure Application rate

Catheter ablation for atrial fibrillation

In 2010, 8.8 million of patients had atrial fibrillation in the Europe Union. A projection study estimated a total of 17.9 million of patients at 2060 [5].

Paravalvular leakage repair

Affects 5%-17% of all implanted prosthetic heart valves [6].

Percutaneous mitral valve replacement

Mitral valve diseases present an estimated prevalence of 7% in subjects ≥75 years old [7].

2. Atrial anatomy

Transseptal access of the LA requires large knowledge and experience of the atria

anatomy, particularly the IAS wall. Moreover, the physician should be aware of possible

anatomic variations to correct and safe recognition of the optimal puncture position [8]. As

such, in this section an overview of the atria anatomy and possible variations is presented.

The RA shows larger volume and thinner walls (approximately 2 mm) than LA.

Anatomically, the superior RA is composed by the superior vena cava (SVC) and the right atrial

appendage [9]. The inferior RA is constituted by the inferior vena cava (IVC) and the tricuspid

valve. The SVC receives the blood from the superior part of the body, while the IVC returns the

blood from the inferior one. The tricuspid valve controls the blood circulation between the RA

and the right ventricle (RV). Furthermore, particular attention with the coronary sinus (CS)

position is required. The CS is a set of vessels that collect blood from the myocardium draining

into the RA. This structure is positioned between the orifice of the IVC and the tricuspid valve

[9, 10].

On the other hand, the LA is smaller with thicker walls (approximately 3 mm). It presents a

cuboidal shape, being limited superiorly by four pulmonary veins and the left atrial appendage

(LAA) [9]. Inferiorly, the mitral valve (MV) controls the blood circulation between the left atria

and left ventricle [10]. As a final remark, it should be noticed that: 1) the aorta and pulmonary

artery cover the LA externally [11]; and 2) the LA is separated from the esophagus by a thin

fibrous pericardium [11].

The interatrial septal wall (IAS) is found between the two atria. The IAS is formed from the

fusion of the septum primum (LA septum) and the septum secundum (RA septum) [1]. The

fusion region is termed limbus (or “true septum”) presenting a larger thickness. However, a

depression can be detected in the middle of the limbus, which is called fossa ovalis (FO) [9].

The FO is the thinnest region of the IAS and it is composed by thin fibrous tissue [9].

Additionally, it has an oval or circular shape and can only be detected from the RA [1].

Anatomically, the FO presents an expected average area between 1.5-2.4 cm2 and it is situated

at the lower part of the septum, between the IVC and the CS [1]. Since lowest thickness is

found at the FO, transseptal access of the LA is traditionally performed through this structure.

[12]. Beyond the FO, the His bundle can be also detected at the inferior IAS wall and it is

composed by myocardial cells that propagate the electric pulse from the atrioventricular node

to the ventricles [9].

In Table 2 is presented an overview of the most common anatomic variations of the atria

region. Note that different LA access site is required when an abnormal anatomy is identified.

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These modifications are crucial to ensure the maximum safety of the procedure and reduce

the number of complications [14].

3. Traditional transseptal puncture technique

In the current section, a briefly description of the TSP procedure is presented. Moreover,

an overview of the common procedural complications is stated.

The TSP procedure has been widely explained in literature [1, 3, 17], reporting the

guidance equipment and catheters used to safely puncture the IAS wall. The technique is

guided using bi-dimensional fluoroscopy and is performed using a mechanical Brockenbrough

needle (BRK, St. Jude Medical, Minneapolis, MN, USA). Furthermore, several auxiliary

catheters are used to prevent puncture of vital structures. For instance, catheters at the aorta,

CS and His bundle are commonly used. Regarding the procedural time, frequently 1 to 15

minutes are required to perform this task. [15, 16, 18-20].

The procedure starts with the insertion of a guidewire (0.032-0.035 inch) into the IVC

using the right femoral vein access. This step is guided using a anterioposterior fluoroscopy

view. The guidewire is used to define a safe route between the femoral vein and the SVC. A

dilator and sheath are also positioned into the SVC using the guidewire. At this stage, the

guidewire is replaced by the BRK needle, maintaining it inside the sheath to prevent

inadvertent punctures. Then, the assembly (needle, sheath and dilator) is positioned at the FO

region. The assembly is rotated to 4-5 o’clock position and posteriorly pulled-down using a left

anterior oblique (LAO) fluoroscopy view. At this point, two movements will be detected: the

first indicates the entrance of the assembly into the RA; and the second, which is less

perceptible, occurs when the assembly is inside the FO region. A confirmation of the assembly

Table 2 – Overview of the main anatomic variations of the atria.

Anatomic variations

Description Difficulties Solution

Patent foramen

ovale (PFO)

- Direct route between the RA and the LA (prevalence of 27% of the population) [13]. - LA access without any puncture [13].

Since the PFO is located at the anterior and superior part of the IAS, access to the pulmonary veins are hampered [13, 14].

TSP procedure should be used, even in the presence of PFO [14].

Left atrium dilation

- LA dilation results in a posterior position of the FO [8].

Higher risk of puncture an adjacent structure [8].

Different TSP position should be used [8].

Abnormal mechanical properties of the IAS

- Heart diseases can result in aneurysmal, elastic or thickened IAS wall [15]. - Patients with previous TSP procedure, present a thickened IAS wall [16].

TSP procedure can result in serious complications for the patient, such as, atrial roof puncture or aortic route puncture. Furthermore, TSP procedure can fail [15].

Application of radio-frequency (RF) needles [15].

Abnormal position of

the FO

- Superior position of the FO is detected [11].

Superior LA access reduces the maneuverability of catheters in pulmonary veins and mitral valve procedures [11].

Puncture the inferior part of the FO [11].

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position is achieved using the right anterior oblique (RAO) direction of the fluoroscopic tube.

Since puncture outside the FO increases the risk of perforating vital structures and limits the

maneuverability of the catheter in the LA, confirmation of the needle position should be

performed [11]. Furthermore, a confirmation of the actual position of the aorta, CS and His

bundle is required to ensure safety of the puncture.

Finally, the puncture can be performed and the surgical tool can be introduced into the

LA. The position of the needle is confirmed using the left atria pressure variation or contrast

agents to confirm the needle position. It should be noted that a repetition of the entire

procedure is required when the assembly is not aligned with the FO or when the expert has

doubts about the assembly position.

As a final remark, although low complication and failure rate (approximately 1% of the

procedures [3]) are commonly associated with the TSP, the physician should be aware of:

aortic root puncture, arterial air embolism, pericardial tamponade, right or left atrial wall

puncture, transient ST-segment elevation, pleuritic chest pain, persistence of atrial septal

defect and death as all are complications that can be caused by this intervention [3, 16, 19, 21-

25]. Furthermore, since TSP creates a hole in the IAS, post-procedural complications are

reported, such as persistent iatrogenic atrial septal defects (iASD). iASD can originate serious

complications (e.g. mitral valve calcification, lower cardiac output, increased rate of

paradoxical embolism), consequently requiring a second procedure [26-30].

4. Materials and Methods

In this section, we report the criteria used to identify the relevant works for this review.

4.1. Selection Method

A search was performed on PubMed, Scopus and ISI Web of Sciences databases between

9 of April of 2015 and 10 of April of 2015. The search used the expression “transseptal

puncture”. Note that only works published between January of 2008 and April of 2015 were

considered. As a result, a total of 834 articles were obtained and, posteriorly evaluated.

Figure 1 - Transseptal puncture traditional technique. (a) A catheter (blue) is placed into the SVC; the catheter is pull-down and two movements are detected, namely: (b) entrance into the RA and (c) entrance into FO; (d) after FO identification the puncture is performed.

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4.2. Data Collection and Processing

In all 834 articles, we analyze the title and the abstract. In this step, the follow criteria

were established, namely: 1) the study must be written in English; 2) patents were excluded; 3)

studies with main focus different of the proposed study were excluded. Furthermore, letters

reviews and clinical reports of one difficult procedure were also not used. Table 3 presents an

overview of the excluded reviews. As such, a total of 64 articles were selected for the current

review. As a final remark, Figure 3 presents an overview of the number of studies per year and

the number of selected papers in each of the three databases used.

4.3. Data Analysis

The 65 selected articles (192 results) were completely analyzed and classified into

different categories: incidence studies, intra-procedural guidance techniques, pre-procedural

planning methods and surgical instruments (see Figure 2). A work can be included in more

than one category.

5. Results

In this section an overview of the main topic addressed by the 65 selected articles is

presented.

5.1. Study characteristics

Thirty-seven articles reported TSP procedure previous experience, describing the

technique applied, the number of failures and the complication rate achieved. As a result, a

total of 15904 procedures were reported between 2008 and 2015

Regarding the new strategies proposed to overcome the main limitations of TSP

intervention, twenty-four studies suggested new intra-procedural guidance techniques. These

systems were validated in 958 humans, animal model and in vitro models. Five studies

suggested that pre-procedural planning of the procedure is crucial to identify a “safe puncture

zone”, validating these novel techniques in 211 humans. Finally, twenty-one works focused on

novel surgical equipments. 5269 procedures, animal model experiments and in vitro studies

were used to validate the novel surgical tools.

5.2. Incidence Study

Table 4 presents a review of the total number of TSP procedures performed between 2008

and April of 2015. Note that the procedures were not only performed in normal atria anatomy

situations. Several studies use heterogeneous population, which includes: children’s [31-33],

abnormal atria anatomy [20, 25, 34-41] or patients with previous TSP [15, 16, 24, 42-46]. The

number of puncture attempts, failures and complications were registered. The results show

that approximately 12% of the procedures require more than one puncture attempt to achieve

the FO position, and complications/failures rate are lower than 1% (Table 4).

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Figure 2 - Overview of the methodology used to select the relevant papers for the current review.

Table 3 – Topics addressed in different reviews published between 2008 and 2015.

Year Authors Aims 2014 Matsumoto et al. [2] Recent advances in transseptal left heart interventions. 2012 Kautzner et al. [47] Review of imaging techniques used in LA procedures.

2011 Sy et al. [48] Overview of difficulties and possible solutions throughout

TSP procedure.

2010 Tzeis et al. [49] Exhaustive review of TSP procedure and overview of tips and

caveats with relevant value for safe TSP. 2009 Earley et al. [3] Review of TSP procedure complications and possible solutions.

2008 Babaliaros et al. [1] Review of novel techniques used in TSP intervention and

emerging indications of this intervention. 2008 Ross et al. [17] Overview of transseptal left heart catheterization procedures.

Figure 3 – Results of the search performed on three online databases. (a) Distribution per year of the studies used in the current review. (b) show the number of selected works from PubMed, ISI Web of Knowledge and Scopus when the search expression was “transseptal puncture”. Note that the total number of search results is also presented.

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5.3. Intra-procedural guidance techniques

Although the traditional TSP procedure only uses bidimensional fluoroscopy as unique

guidance strategy [18], several authors proposed the application of new image modalities,

namely: transesophageal (TEE) [35, 50-55], intracardiac echocardiography (ICE) [19, 56-60],

real-time magnetic resonance (MR) [61] and direct color visualization [62]. Furthermore,

needle tracking based on electromagnetic sensors [63] and electroanatomic mapping (EM) [33,

64-69] were also presented. These novel guidance techniques increase the safety of the TSP

procedure [19, 50, 56, 67], reduce or completely eliminate the radiation from the procedure

[33, 56, 57, 63, 64] and remove the contrast injection to confirm correct LA access [57].

Moreover, quickly procedures were performed [57] and a higher success rate in difficult

situations were achieved [19, 50].

As a final remark, Table 5 presents an overview of the different guidance techniques

applied in TSP procedures.

5.4. Pre-procedural planning techniques

Some authors proposed new pre-interventional planning techniques, namely:

identification of a safe zone to perform the puncture [46, 70-72] and identification of the

optimal puncture position, which guarantee maximum catheter dexterity inside the LA [73].

This planning step relies on pre-interventional image acquisition, namely: CT [70, 71, 73],

MR[73] or TEE [46, 72]. The authors agreed that these novel planning methods allow accurate

planning of the TSP procedure, increasing therefore the safety of TSP and reducing

complication and failures rate [70, 73].

As a final remark, Table 6 presents the aims, validation and conclusion of these novel

studies.

5.5. Surgical instruments

In the last years, a high number of studies focused on the traditional BRK needles. This

needle crosses the septum using a mechanical process, based on pressure applied on FO

region. Nonetheless, in abnormal septal wall (e.g. aneurysmal or elastic) high pressure can

result in inadvertent puncture and consequently, intervention complication [15]. As such,

novel transseptal needles were proposed to overcome the limitations of the BRK needle,

namely: RF rigid NRG needle (Baylis Medical) [15, 16, 22, 24, 44, 74-76], RF flexible Toronto

needle (Baylis Medical) [34], electrocautery needle technique [42, 77-80] and coaxial

transseptal (CTS) needle [81].

Furthermore, some authors proposed novel solutions for the remaining surgical

equipment’s, namely: dilator, guidewire and catheters. Thereby, a new dilator approach [21], a

laser catheter and a nitinol guidewire with “J” shape [37, 38, 82] were suggested to prevent

inadvertent puncture and reduce complication rate.

A robotic remote navigation system, based on Sensei framework, was also suggested to

perform safe LA interventions. This system was applied throughout TSP intervention and

ablation of atrial fibrillation [69].

Finally, Table 7 presents an overview of this novel surgical equipment’s.

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Table 4 – Number of TSP, percentage of repeated procedure, failures and complications reported between 2008 and 2015.

Year Authors Number of

TSP Repeated puncture

Failure Complications

2015 Jauvert et al. [34] 225 5.78% 0 3

2014 Alvensleben et al. [31] 365 - 0 8

2014 Koermendy et al. [83] 147 - 4 20

2014 Lehrmann et al. [43] 678 - 0 0

2014 Tang et al. [25] 3452 - 0 10

2014 Unnithan et al. [67] 54 - 0 1

2014 Zellerhoff et al. [40] 39 - 0 1

2013 Chierchia et al. [84] 103 - 0 9

2013 Esch et al. [44] 10 - 1 0

2013 Hsu et al. [16] 72 - 10 2

2013 Katritsis et al. [85] 393 - 0 5

2013 Yao et al. [18] 120 14.17% 5 6

2012 Bayrak et al. [35] 205 46.34% 1 3

2012 Mulder et al. [39] 634 - 4 -

2012 Wang et al. [21] 4443 - 0 27

2012 Yao et al. [36] 539 1.11% 0 0

2011 Abed et al. [79] 543 1.84% 10 10

2011 Fromentin et al. [15] 241 20.33% 0 2

2011 Miyazaki et al. [41] 114 - - 1

2011 Wadehra et al. [37] 210 16.67% 5 0

2011 Winkle et al. [75] 1550 - 13 9

2011 Elayi et al. [32] 13 15.38% 0 0

2010 Haegeli et al. [23] 269 - 0 8

2010 Mitchell-Heggs et al. [19] 79 - 0 9

2010 Schwagten et al. [4] 11 - 1 0

2010 Smelley et al. [24] 41 - 1 0

2010 Wieczorek et al. [38] 158 - 0 0

2009 Ferguson et al. [56] 21 - 0 0

2008 Chierchia et al. [52] 24 0% 0 0

2008 Clark et al. [33] 10 - 0 0

2008 Hu et al. [45] 29 - 0 0

2008 Knecht et al. [42] 269 4.47% 0 0

2008 Knecht et al. [14] 203 35.96% 0 0

2008 Lakkireddy et al. [20] 90 - 1 4

2008 Saliba et al.[69] 40 - 2 1

2008 Wu et al. [55] 468 - 0 1

2008 Tomlinson et al. [46] 42 35.71% 0 4

Mean (%): 12.41% 0.37 0.91

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Table 5 – Novel intra-procedural guidance techniques applied in TSP procedures between 2008 and 2015.

Year Authors Aims Guidance technique Validation Conclusion

2015 Gafoor et al. [51] Use of EchoNavigator in TSP. 3D TEE fused with

fluoroscopy. - This system showed potential for safe and simple TSP procedure.

2014 Faletra et al. [53] Application of 3D TEE in TSP. 3D TEE - 3D TEE easies TSP procedure when compared with remaining guidance

approach, such as 2D TEE or fluoroscopy.

2014 Jeevan et al. [63] Validation of a new image-guided

method for radiation-free TSP. Electromagnetic sensor

fused with MRI. 1 phantom

This system reduced the procedure time, had no learning curve and can reduce the number of complications.

2014 Mah et al. [68] EM with ICE to simple TSP. EM combined with ICE 25 patients The proposed system reduced the radiation exposure and time.

2014 Pavlović et al. [66] Strategy to simple reaccess of FO

without radiation. EM (Carto 3). 25 patients A radiation-free recrossing of the IAS wall was achieved.

2014 Unnithan et al. [67] Strategy to simple reaccess of FO

without radiation. EM (3D NavX). 54 patients The method reduced the time that catheter dwells in LA.

2013 Nguyen et al. [65] Strategy to manual or automatic reaccess of FO without radiation.

EM (Ensite/NavX). 5 patients Manual and automatic reaccess of the LA is viable and fast. Moreover,

radiation exposure was removed.

2013 Ruisi et al. [58] Application of ICE in TSP procedure ICE - ICE can be used to guide TSP.

2013 Russo et al. [59] Application of ICE in TSP procedure ICE - ICE contributes to improve the efficacy of TSP procedure.

2013 Yao et al. [18] Validation of a new TSP procedure. Fluoroscopy. 120 patients This method was simple, safe and economic.

2012 Bayrak et al. [35] Application of 2D TEE in TSP. 2D-TEE and fluoroscopy. 105 patients A correct puncture position was achieved.

2012 Biermann et al. [60] Application of ICE in TSP procedure ICE - ICE contributed to improve the efficacy of TSP procedure.

2011 Faletra et al. [50] Advantages of 3D-TEE in TSP. 3D TEE. - 3D TEE allows simple FO identification.

2011 Stec et al. [54] Application of micro-TEE in TSP. Micro-TEE probe 12 patients Micro-TEE can be used to guide TSP in non-sedated patients.

2010 Liang et al. [57] Comparison between mechanical

versus phase-array ICE in TSP. ICE. 6 patients

Mechanical ICE has a better image of the FO, being therefore more adequate to perform TSP.

2010 Mitchell-Heggs et al.

[19] Advantages of ICE in TSP. ICE. 79 patients A safe and well tolerated guidance of TSP was achieved.

2009 Ferguson et al. [56] Application of ICE to perform TSP. ICE. 21 patients Succeed TSP was achieved using ICE guidance technique.

2008 Chierchia et al. [52] Application of 3D-TEE in TSP 3D TEE 24 patients TEE eased TSP. Moreover, lower procedural time was reported.

2008 Clark et al. [33] EM combined with TEE in TSP can

be used to perform TSP EM combined with TEE 10 patients

The proposed method can be used to eliminate the fluoroscopy used throughout TSP procedure.

2008 Elagha et al. [61] Application real-time MRI in TSP. Real-time MRI. 7 animals MRI-guided can be used to perform safe TSP procedure.

2008 Saliba et al. [69] Combination of EM and ICE in TSP. EM and ICE 40 patients This system ensured safe TSP procedure.

2008 Shepherd et al. [64] Application of EM mapping in TSP. EM (EnSite NavX). - EM can reduce the fluoroscopy time requires in TSP procedures.

2008 Thiagalingam et al.[62] Full color visualization of FO. Fiber optic and fluoroscopy. 6 swine Direct full color visualization can be used to identify FO.

2008 Wu et al. [55] Application of TEE in TSP. TEE 468 patients TEE eased the identification of optimal puncture position.

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Table 6 – Pre-procedural planning methods applied in TSP procedures between 2008 and 2015.

Year Authors Aims Planning method Validation Conclusion

2013 Schernthaner et al. [72] Preprocedural TEE can be used to identify abnormal atria anatomy

TEE 100 patients Pre-planning TEE provided accurate information of patient-specific anatomy, which increases the efficacy and safety of TSP procedure.

2012 Wagdi et al. [70] Identification of a “safe zone” to

perform TSP. CT. 20 patients

CT can be used to predict feasibility of TSP procedure. Moreover, CT image can be used to identify a safe puncture region.

2011 Jayender et al. [73] Identification of optimal puncture

position. MR/CT. One dataset

A safe puncture position, that ensures maximum dexterity of catheter, was achieved.

2011 Verma et al. [71] Identification of FO region in CT. CT and EM (Ensite NavX). 49 patients It was possible to detect FO in CT. Confirmation of the FO position

was performed using intra-procedural EM.

2008 Tomlinson et al. [46] FO thickness is a predictor of

difficult TSP procedure. TEE. 42 patients

No relation was found between difficult TSP procedure and FO thickness. The only valid predictor was the presence of diabetes.

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Table 7 - Surgical instruments used in various TSP works between 2008 and April of 2015.

Year Authors Aims Instruments/Methods Validation Conclusion

2015 Giudici et al. [82] Experience with nitinol guidewire. Nitinol guidewire. 100 patients This method is simple, inexpensive, quick and safe.

2015 Jauvert et al. [34] Evaluate the safety of a new RF

powered flexible needle. RF powered flexible

needle and BRK needle. 125 patients Flexible needle was safer and more efficient than BRK needle.

2014 Karagöz et al. [76] Advantages of NRG needle. NRG and BRK needle. 3 patients NRG needle eased the TSP procedure.

2013 Esch et al. [44] Application of RF needle in patients

with congenital heart disease. NRG and BRK needle. 10 patients

NRG needle can be used to LA access in patients with congenital heart disease, including cases where BRK needle failed.

2013 Hsu et al. [16] Comparison of NRG and BRK needle. NRG and BRK needle. 72 patients NRG needle allowed shorter procedure time and lower failure rate.

2012 Greenstein et al. [80] Difference of tissue coring between electrocautery and traditional TSP.

Electrocautery and traditional TSP.

Swine hearts Similar number of tissue coring was achieved by the two

techniques.

2012 Wang et al. [21] Comparison of dilator method with the traditional puncture strategy.

New dilator method and traditional TSP.

2292 patients The new dilator technique was safer than the traditional one. However, the novel method required longer procedure time.

2011 Abed et al. [79] Comparison between electrocautery

techniques and traditional one. Electrocautery technique

and BRK needle. 10 patients

Electrocautery method was safe and cost-effective when compared with traditional one.

2011 Feld et al. [22] Comparison of NRG and BRK needle. NRG RF and BRK needle. In vitro NRG needle appears to be safer than traditional needle.

2011 Fromentin et al. [15] Comparison of NRG and BRK needle. NRG RF and BRK needle. 241 patients NRG needle showed superior performance than traditional needle.

2011 Uchida et al. [81] Validation of a novel CTS needle. CTS needle Animal model CTS needle can perform safe TSP in animal model, even in situations

where the BRK needle failed.

2011 Wadehra et al. [37] Assess safety and efficacy of a novel

puncture method. Nitinol guidewire and

BRK needle. 210 patients The new method showed high success rate.

2011 Winkle et al. [75] Comparison of NRG and BRK needle. NRG RF and BRK needle. 1167 patients NRG needle showed performance than traditional needle.

2010 Capulzini et al. [78] Comparison of electrocautery

technique and traditional needle. Electrocautery technique

and BRK needle. 162 patients

Electrocautery method is a safe and reproducible technique to perform TSP.

2010 Crystal et al. [74] Validation of NRG needle. NRG needle Animal model RF needle eased TSP procedure.

2010 Ponti et al. [86] Comparison of a novel transseptal guidewire and traditional method.

Nitinol guidewire. 19 patients The novel guidewire eased TSP procedure in 23% of the patients.

2010 Smelley et al. [24] Validation of NRG needle. NRG needle. 41 patients NRG needle was safe with low failure rate.

2010 Wieczorek et al. [38] Validation of a novel nitinol guidewire

in TSP procedure. Nitinol guidewire and

BRK needle. 158 patients

Nitinol guidewire appears to be safe and effective in a subset of patients at higher risk for complications.

2009 McWilliams et al. [77] Comparison of electrocautery

technique and traditional needle. Electrocautery technique

and BRK needle. 350

procedures The electrocautery technique eased TSP procedure.

2008 Knecht et al. [42] Application of electrocautery needle

technique in TSP Electrocautery needle

technique 269

procedures Electrocautery provided simple and safe LA access, even in

situations where BRK needle failed.

2008 Saliba et al. [69] Robotic remote steerable sheath

system to perform TSP puncture and ablation of atrial fibrillation

Robotic remove navigation system

(Sensei system) 40 patients

This new system was safe with similar results when compared with the conventional approach.

13

6. Discussion

6.1. Incidence Study

Between 2008 and 2015, an average complication and failure rate lower than 1% was

reported by a large number of authors (see Table 4). These results are in accordance with

previous studies [3], proving that TSP is a safe and feasible technique in clinical practice.

Furthermore, we present the number of situations where a second attempt was required to

correct the alignment between the needle and FO. Approximately 12% of the procedures

required more than one puncture attempt, which increases the procedural time and the

radiation exposure. This last result could indicate that FO recognition/puncture is not

straightforward, claiming for novel guidance strategies and smart surgical equipment [75-77].

In 2012, Yao et al. published a clinical experience article about TSP procedure [78]. A total

of 539 puncture were reported, with success of 100% and first attempt puncture of 98.9%.

Similarly, Alvensleben et al. and Elayi et al. proved that TSP can be safely applied on children’s

[76, 79] with a low complication rate (0.3%, [76]). Yao et al. and Bayrak et al. discussed the

difficulties of TSP on unexperienced hands [18, 35], proving that higher failure rate and large

procedural time are achieved by trainees. Moreover, Schwagten et al. presented an interesting

comparison between LA access through TSP and TA approach. 22 patients were used in this

experiment. Regarding the results, similar complication and failure rate was achieved by the

two strategies. Note that one and two failures were registered with TSP and TA approach,

respectively [4].

Several authors focused on clinical studies to identify the main complication and

limitations of TSP procedure [14, 25, 40, 43, 45, 83-85]. The authors reported that:

1) cardiac tamponade is the main cause of complications and catheter technology should

be improved to reduce the procedure complications [40, 85];

2) any consensus was found between LA access through PFO or TSP procedure. Lehrmann

et al. and Knecht et al. agreed that TSP procedure results in lower complication rate

[43] and allow simple maneuverability of the catheter inside the LA [14] when compared

with PFO access. However, Koermendy et al. and Miyazaki et al. published clinical

reports proving that LA access through PFO is safe with higher success rate and lower

complication rate when compared with TSP [41, 83];

3) repeated TSP presented higher complication rate and higher number of puncture

attempts [45] when compared with patients without any previous procedure;

4) anterior, medial and posterior FO are the optimal puncture position, with equal

complication rate and maximum catheter dexterity [84].

In order to ease left heart procedures, multiple catheters placed through double TSP was

suggested [20, 23]. Haegeli et al. performed 269 procedures using double puncture and low

complication rate (approximately 3%) was reported [23]. Similarly, Lakkireddy et al. applied

the same technique in 90 patients with only one failure and a complication rate of 4% [20]. As

such, the authors agreed that double TSP increases the catheters maneuverability inside the

LA [23].

Finally, a high number of studies focused on novel TSP techniques and its comparison

against the traditional technique [15, 16, 19, 21, 23, 24, 33, 34, 37, 38, 44, 52, 56, 67, 69, 75,

79]. The comparison was performed in a high number of patients and the authors proved that

new methods (e.g. radio-frequency needles, guidance with ICE and TEE) reduce the number of

14

complication and failure rate. Additionally, a reduction of the procedural time and radiation

exposure was commonly achieved.

6.2.Intra-procedural guidance techniques

Several authors proposed novel image guidance techniques, based on TEE or ICE, to

overcome the main limitations of the fluoroscopy-based procedures, namely: 1) bidimensional

acquisition with low contrast between the relevant structures and the neighbors; and 2)

continuous radiation exposure.

TEE is a real-time imaging technique where a specialized probe is advanced into the patient

esophageous. Note that general anesthesia is required. Since the transducer is positioned near

the cardiac structure, a clear (2D or 3D) image of the relevant structures is obtained.

Nonetheless, a small field of view of the region of interest is obtained.

Wu et al. and Chierchia et al. suggested the application of 2D [55] and 3D [52] TEE,

respectively, in TSP procedure to correct the alignment between the needle and FO position.

The authors validated this novel image guidance approach in humans. A low complication rate

and any failure were reported, proving therefore the safety and feasibility of the new method

in clinical practice. Furthermore, lower procedural time were reported [52, 55]. Faletra et al.

presented extended reports about atria anatomy interpretation in real-time 3D TEE [50, 53].

They proposed that 3D TEE is useful in pre-procedural planning step and during the TSP

procedure, due to the clear definition of the “true” septum border. Moreover, Bayrak et al.

proved that TEE allows simple recognition of the anatomical structures and it is essential to

safe TSP in unexperienced hands [35]. Finally, Gafoor et al. recently proposed the application

of the novel EchoNavigator system (Philips Inc., Amsterdam, Netherlands) on the TSP

procedure [51]. The EchoNavigator automatically combines 3D TEE image with 2D fluoroscopy,

which allows simple catheter guidance until the target site. Note that 3D TEE and fluoroscopy

ease FO recognition and instruments tracking/identification, respectively. As such, the

physician can introduce several landmarks on the 3D image obtained from TEE (e.g. optimal

puncture position) and accurately visualize them in the traditional fluoroscopic image.

Although this system presented promising results, any validation study was reported [51].

Since TEE requires high level of sedation with high costs, micro-TEE probe was suggested to

overcome this limitation. Stec et al. applied the novel method in 12 non-sedated patients

without any failure. Moreover, a clear image of IAS wall was achieved, proving that this image

guidance approach can be safely used in TSP procedure [54].

Similarly, ICE imaging was also proposed as an interesting solution for inexpensive and safe

TSP procedure. This technique acquires real-time ultrasound imaging through an instrumented

catheter positioned into the RA. This catheter has an ultrasound transducer at the catheter tip

and high sedation level is not required. Mitchell-Heggs et al. applied ICE guidance in 79

procedures with a complication rate of 11%. Furthermore, the authors also reported that this

image technique can be used to confirm correct needle position inside the LA [19]. Similarly,

Ferguson et al. proved that ICE guarantee safe TSP, through the application of this technique in

21 situations without any complication [56]. Liang et al. compared two ICE techniques in order

to identify the optimal strategy for TSP procedure, namely mechanical ICE and phase-array ICE.

Mechanical ICE uses a non-flexible catheter, with a bidimensional image generated

perpendicularly to the catheter. In opposition, phase-array ICE uses a flexible catheter, shows

color Doppler functions and uses multiple transducers controlled electronically to produce a

15

wedge shaped image. Both methods showed a clear image of the IAS and FO [57]. However,

since mechanical ICE has a better near field view, needle guidance inside the RA is simpler.

Additionally, mechanical ICE is a lower cost strategy [57]. Finally, several authors presented

interesting extended reports about ICE image guidance during TSP procedure, where a

detailed explanation about the image acquisition strategy and atria anatomy interpretation in

ICE is presented. [58-60]. Furthermore, the authors also mentioned that ICE is crucial for

identification/prediction of adverse events, reducing therefore the number of complications

and failures [60].

Elagha et al. and Thiagalingam et al. proposed different image-guidance strategies based on

real-time MRI [61] and direct full color visualization [62], respectively. Regarding the first

strategy, the authors applied an interactive, multi-slice real-time MRI using steady free

precession pulse sequences. Since the patient is positioned inside the MRI machine, some

equipment (e.g. catheters) was modified. As a result, the authors proved that transseptal

needle and FO region can be accurately identified with this imaging technique. The method

was tested in animal models without any complication [61]. Thiagalingam et al. proposed

direct visualization of the IAS through a fiber optic catheter. A real-time visualization of IAS

was achieved through a connection between the fiber optic and a monitor. Moreover, a

pressurized bag of saline solution, connected to the fiber optic, was used to clean the blood

from the top of the camera. TSP was performed in animal models without any complication.

Furthermore, post-mortem analysis showed a high correlation between puncture site and real

FO position. As a final remark, although these two methodologies presented large potential to

a safe and quick guidance of the TSP, human validation is missing [61, 62].

Instead of novel image guidance methods, Yao et al. proposed a modification of the

traditional TSP procedure. Similarly to the traditional approach, this new method is also guided

by fluoroscopy, being therefore an inexpensive and attractive solution [18]. Nevertheless, in

this solution a distal CS catheter is used and positioned on the lateral marginal of the heart,

consequently defining the level of FO at posterior-anterior projection of fluoroscopy. As such,

after an initial alignment between the needle and FO, using the traditional TSP procedure, a

confirmation of the needle site is performed using the CS catheter site. In this confirmation,

the physician verifies if the TSP needle is positioned between the distal CS catheter and the

peak posterior margin of LA at RAO direction of fluoroscopy. Finally, the needle can safely

puncture the FO until LA. The current method was applied in 120 patients with mean

complication rate and failure rate of 5% and 4%, respectively [18].

Several studies proposed novel guidance methodologies based on electroanatomic

mapping (EM) [33, 64, 68, 69] and electromagnetic sensors [63], respectively. The authors

suggested that fluoroscopy time can be notably reduced [64, 68] or removed [33] from TSP

procedure, therefore presenting clear advantages for the physician and the patient. Shepherd

et al. used the EM technique to generate a 3D model of the atria and to guide the transseptal

needle until the FO. Nonetheless, any clinical validation was performed. Moreover, since EM

technique does not provide real-time geometries, a sub-optimal guidance approach was

achieved [64]. As such, Mah et al. suggested the combination of EM and ICE to reduce the

fluoroscopy exposure time. The proposed approach was applied in clinical practice, where a

significant reduction of the fluoroscopy dose and time was observed [68]. Similarly, Saliba et

al. applied the same technique (EM combined with ICE) in a robotic remote navigation system

16

to perform TSP procedure. The entire framework was tested in 40 patients, showing similar

complication and failure results when compared with the traditional approach [69].

Instead of ICE imaging, Clark et al. presented a novel system where EM data is fused with

real-time TEE. The optimal puncture is performed in two steps: 1) identification of the optimal

puncture position and adverse events using the RA geometry generated by EM; 2)

confirmation of the correct alignment between the needle and puncture site using TEE. The

proposed system was applied in 10 patients without any complication or failure. Furthermore,

fluoroscopy time and exposure was not required [33]. Finally, Jeevan et al. proposed a

different strategy to guide the physician throughout transseptal puncture procedure. In this

strategy, an electromagnetic sensor was positioned on the tip of the catheter and it was rigidly

aligned with a patient specific atrial model, which was obtained from a pre-interventional MRI.

This register was performed through a set of fiducial markers positioned on the real and virtual

atria model. Note that the fossa ovalis position is also represented by a specific fiducial

marker. As such, during the intervention the electromagnetic system indicates the optimal

catheter trajectory until the puncture site. The current system was simulated in one phantom

model, being the procedure performed quickly without any complication. However, this

system was only tested in static models being far from being applied in real situations [63].

Recent studies suggested that left-sided catheter dwelling time appears to be associated

with bleeding, clotting, endothelial dysfunction or char particle embolization [67]. As such,

multiple LA access through TSP is required to reduce the catheter dwelling time into LA, and

consequently reduce the abovementioned complications [67, 87]. However, multiple LA access

is time-consuming, frustrating, require large radiation dose and can originate serious

complications [65]. Interesting solutions to quick and safe LA reaccess without any radiation

were proposed in [65-67]. All the strategies use EM to generate geometry of the atria region

and create a marker of the TSP site. Unnithan et al. and Pavlović et al. validated this

methodology in 10 and 5 patients, respectively. Quick access without any complication was

reported (approximately 14 seconds) [66, 67]. Additionally, Nguyen et al. proposed a new

remote magnetic catheter navigator system that allows “manual” and “automatic” LA reaccess

[65]. The automatic remote navigator system relies on 8 electromagnetics positioned along the

patient. These electromagnetics will modify the magnetic field applied, when a correction of

needle position or pose is required to achieve the target site. This technique was applied with

success in 5 patients, taking 6.2±8.1 seconds and 30.4±28.4 seconds in automatic and manual

operation mode, respectively [65].

6.3. Pre-procedural planning techniques

The novel pre-procedural planning methods for transseptal puncture procedure focused on

pre-interventional imaging, namely: CT [70, 73], MR [73] or TEE [46, 72]. Wagdi et al. reported

that TSP is challenging in situations where larger devices sizes (e.g. amplatzer) have been

applied to interatrial septal communication closure. As such, they suggested the analysis of a

pre-interventional CT dataset to define a “safe zone” for TSP. Note that the identification of

this “safe zone” will be crucial to assess the feasibility of the procedure. This study was

performed on 20 patients, and the results proved that CT dataset can predict the feasibility

and safety of TSP. Similarly, Schernthaner et al. applied TEE imaging to predict the feasibility of

TSP, proving that TEE can be used to identify patients with abnormal IAS wall anatomy [72].

Tomlinson et al. suggested that FO thickness is a predictor of the difficulty of TSP procedure.

17

Thus, since the wall thickness can be easily observed in TEE images, a total of 42 patients were

assessed by ultrasound imaging and posteriorly classified (difficult or not difficult procedure)

during the pre-procedural planning phase. This initial classification was subsequently

compared with the difficulty of the real procedure, being not found any correlation between

wall thickness and difficult procedure. Finally, Jayender et al. proposed a novel approach for

optimal puncture location estimation. This strategy combines pre-interventional anatomical

models with a mechanical model of the catheter to simulate the puncture procedure. As such,

a finite element method was used to estimate the optimal puncturing site based on the

thickness of the septal wall and the mechanical maneuverability of the catheter at all the

positions of the LA. [73]. The current system was only tested in one offline dataset, missing

application in clinical practice.

6.4. Surgical instruments

New surgical instruments were also presented to increase the efficiency of the TSP, with a

notable number of works focused on the transseptal needles. Although the mechanical BRK

needle appears to be safe in non-complex procedures, the same is not observed in abnormal

atria anatomy or in patients with previous procedure. As such, NRG needles [15, 16, 22, 24, 34,

44, 74-76] and electrocautery needles [42, 77-80] were proposed.

NRG is a rigid needle that uses RF energy to diminish the septal wall resistance, reducing

therefore the mechanical force required for FO puncture. This needle presents a novel design,

with an oval tip to prevent inadvertent puncture. Furthermore, a radiopaque marker was

incorporated inside this equipment to simple needle guidance in fluoroscopy-based methods

[22]. Regarding the clinical practice, any significant modification of the traditional puncture

procedure is required, easing therefore the introduction of this new instrument [15].

In 2010, Crystal et al. and Smelley et al. demonstrated that NRG needles can be used to

perform safe TSP, principally in difficult procedures [24, 74]. The method was validated in: 1)

animal model [74]; and 2) 35 patients [24]. Although animals with complex anatomy (e.g. PFO)

were used, any complication was found [74]. Regarding the clinical validation, only one failure

was registered. As such, the results showed that NRG needle could be used to perform safe

TSP even in abnormal atria anatomy [24, 74].

Subsequently, several authors presented large clinical studies where a comparison between

NRG needle and the conventional one is performed [15, 16, 34, 44, 75, 76, 88]. The authors

agreed that NRG reduces the procedural time, the complication rate, the failure rate and

facilitates the procedure in presence of complex anatomies when compared with the

traditional strategy [15, 44, 75, 76]. Note that randomized single blinded studies have also

been used to validate the abovementioned conclusions [16]. Moreover, Feld et al. proved that

BRK needle can introduce plastic particles into the circulatory system of the patient, which can

originate microinfarcts and left ventricular dysfunction. These particles are created due to a

process of skiving when the needle is advanced along the plastic dilator. NRG needle was also

tested and any plastic particle was found [22]. Although NRG needle appears to present a

superior performance when compared with the traditional equipment, several theoretically

risk should be considered, namely: 1) inadvertent cardiac puncture using RF can result in

greater consequences for the patient; 2) puncture site is less likely to close spontaneously; and

3) the RF puncture can be more traumatic for the FO [24].

18

Recently, a novel RF powered flexible needle, termed Toronto needle was proposed [34].

This equipment presents: 1) an active operating mode based on RF energy; and 2) a novel

catheter design which guarantees safe puncture of the FO and prevent inadvertent puncture

thanks a flexible catheter with large J shaped distal curve. Jauvert et al. compared the Toronto

and BRK needle in humans. 125 punctures were performed with Toronto needle, and 100

punctures with the traditional approach (BRK needle). The results demonstrated that Toronto

needle has a superior performance, lower number of failures (5% for BRK and 0% for Toronto

needle) and lower complications rate (7% for BRK and 0% for Toronto needle) rate when

compared with traditional approach [34].

Electrocautery pen combined with traditional BRK needle was also proposed to ease septal

wall cross [42, 77-80]. In this method, the traditional TSP procedure is initially performed to

align the needle with the FO region. Subsequently, the cautery pen (15-20W) is applied (during

approximately 1-2 s) on the proximal portion of the needle [77, 78], cauterizing the FO region

and reducing consequently, the pressure required to perform the FO cross. Similarly to the

NRG and Toronto needle, this novel approach reduces the complication and failure rate when

compared with the BRK needle, mainly in highly elastic, aneurysmal, or fibrotic septal wall [42,

77-79]. Finally, Greenstein et al. compared both techniques to verify the incidence of tissue

coring into the needle tip [80]. It should be noticed that coring of the septal wall can originate

complications, such as systematic embolization. The study was performed in animal models

and the results showed a similar number of tissues coring (approximately 35% of the

punctures) with both approaches, raising questions about the real safety of the TSP

intervention.

On the other hand, Uchida et al. proposed a novel mechanical transseptal needle, termed

coaxial TS needle. This novel needle is longer than the traditional one, showing high safety and

feasibility in 10 punctures performed at 10 animal models. Note that LA access was not

achieved with the traditional needle in the abovementioned animal models [81].

Although several authors proposed and validated novel transseptal needle to safe TSP

procedure, novel solutions were also presented for the remaining equipment, namely: nitinol

guidewire [37, 38, 82, 86] and laser catheters [61]. Nitinol guidewire (SafeSeptTM, Pressure

Products Inc., San Pedro, USA) presents a “J” preformed with 0.014″ wire and sharp-distal tip.

This novel equipment is positioned inside the needle assuming two different shapes, namely:

1) a straight shape when the guidewire is completely positioned inside the needle; and 2) a “J”

shape when the guidewire is outside of the needle. The straight guidewire shape facilitates

catheter manipulation and “J” guidewire shape prevents inadvertent punctures. Furthermore

this novel guidewire has a radiopaque marker at the guidewire tip, easing therefore

instrument identification in fluoroscopy. This novel solution was compared with the traditional

TSP strategies in humans, showing a high success rate even in difficult procedures [37, 38, 82,

86]. Moreover, Wadehra et al. suggested that the nitinol guidewire is a safe and useful

alternative for the expensive TSP procedures based on 3D image guidance [37].

Elagha et al. proposed a laser catheter for TSP procedure guided by real-time MRI. A

receiver coil, positioned at the catheter tip, was used to generate a bright spot that can be

easily detected on MRI. This new system was validated in animal model, proving that the laser

catheter can be accurately detected in real-time MRI [61]. Furthermore, the novel system

proved to be safe and quick for TSP procedures.

19

Some authors suggested that robotic remote navigation system (Sensei) can be used in LA

interventions, such as transseptal puncture. The robotic system allows better catheter

stability, precise positioning of the surgical equipment and simple catheter maneuverability,

increasing therefore the safety of the procedures. Clinical validation was reported, being

registered only one intra-procedural complication [69].

Finally, Wang et al. proposed a different TSP strategy, where different surgical tool

configuration is used. This novel method, termed dilator method, presents the follow

modifications: 1) the outer sheath was removed from the procedure, being only required the

dilator and a transseptal needle; and 2) the transseptal needle was kept inside the dilator

during the entire guidance procedure [21]. As such, the identification of the lip edge of the FO

was performed using the dilator. Since the dilator presents a blunt tip, FO identification was

eased. A comparison between the novel method and the traditional one was performed in a

total of 4443 patients. The results suggested that the dilator technique is much safer than the

traditional approach, with a reduction of the number of severe complications (see Table 4).

Nevertheless, an increase of the procedure time and radiation time was registered with this

novel approach [21].

7. Conclusions

The current study presents an overview of novel techniques/frameworks recently applied in

TSP procedure. TSP is safe and feasible in clinical practice, with complication and failure rate

lower than 1% of the total number of interventions. Nonetheless, the traditional procedure

uses radiation and it is dependent of the physician experience. Since TSP is entirely based on

experience, serious complications for the patient can occur, primarily in the presence of

abnormal IAS wall anatomy, showing that a sub-optimal methodology is being used to access

the left heart.

The novel RF needles or the recent 3D guidance approaches showed a notable reduction of

procedural time and radiation exposure time. A lower number of procedural complications and

failures were also reported even in the presence of complex atria anatomy, proving the

advantages of these novel methodologies throughout the puncture intervention. Furthermore,

since both systems can be easily adapted into the surgical room, their future application in a

large number of LA access interventions is expected. Nonetheless, exhaustive clinical validation

of several novel techniques is still missing.

Finally, pre-procedural planning based on high-resolution imaging appears to be a crucial

stage to predict the feasibility of the TSP procedure. Moreover, these strategies can be used to

identify a safe puncture zone that guarantees maximum catheter dexterity throughout the

remaining LA intervention.

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