Introduction

Endomyocardial biopsy is the current gold standard for work-up of non-ischemic myocardial disease [1–5]. As a recent analysis of 755 procedures and 6371 biopsy samples demonstrated that LV-EMB is associated with a significantly lower procedural risk, while yielding similar results as RV or biventricular EMB [6], isolated LV-EMB seems to be the strategy of choice if EMB work-up is needed. However, for this strategy, transarterial access is required. The commonly used transfemoral access is associated with bleeding from the access site due to the need for large diameter sheaths, and needs strict post-procedural immobilization. Thus, a current joint scientific statement of the American Heart Association, the American College of Cardiology, and the European Society of Cardiology concluded that newer interventional techniques are desirable to improve the safety and efficacy of EMB [7].

Arterial access via the radial artery is increasingly used for diagnostic coronary angiography and percutaneous coronary interventions. It is associated with fewer vascular access site complications, and has been shown to reduce major bleeding when compared to the femoral approach [8–10]. While, being accepted as an equal alternative for coronary interventions, it is still believed to be restricted to this field due to the limited capability of the radial artery to bear large diameter guiding catheters such as needed for EMB. Thus, our aim was to provide a first safety and efficacy assessment for a systematic transradial approach for left ventricular EMB using a new highly hydrophilic sheathless guiding catheter [11].

Methods

Patient population

From March 2012 to September 2014, all patients presenting to our outpatient clinic for EMB work-up of myocardial disease were screened for EMB via transradial access using a modified Allen Test (n = 74, see Fig. 1). In total n = 42 consecutive patients with normal Allen Test gave informed consent for transradial biopsy, and were included in the study (Fig. 1). In the first patients duplex sonography of the radial arteries was additionally performed before EMB to rule out vascular malformations. Further information on the patient population is given in Table 1.

Fig. 1
figure 1

Patient screening and inclusion flow-chart of the present study

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Table 1 Clinical characteristics
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Transradial coronary angiography and right heart catheterization

All procedures were performed by experienced interventional cardiologists used to work with transradial access on a regular basis. Where clinically indicated, right heart catheterization was performed using an appropriate vein of either the right or the left arm as described elsewhere [1–12]. Left heart catheterization was performed via the right radial artery using a routine transradial access protocol. In brief, after local anesthesia with 2 ml of 0.1 % Mecaine a dedicated 5F transradial sheath was introduced into the right radial artery. Verapamil (2.5 mg) and nitroglycerin (0.2 ml) were administered prior to catheter insertion to prevent radial spasm. Subjects received 5000 units of unfractioned heparin and coronary angiography was performed using either dedicated transradial catheters (TIGER® I or II, Terumo, Tokyo, Japan) or standard Judkins left or right curves. If microvascular or epicardial coronary spasm was considered as a differential diagnosis, an additional coronary acetylcholine test was performed [13].

Radial EMB procedure

With no dedicated material for transradial EMB, we first reviewed the equipment available. The 7F sheath routinely used at our institution has an outer diameter of 3.1 mm which is generally regarded as too large for radial access, at least if applied to a majority of individuals. Thus, we decided to use large bore sheathless guiding catheters (EauCath®, ASAHI Intec, Tokyo, Japan). These guiding catheters in the 7.5F configuration offer a large inner diameter of 2.057 mm while featuring an outer diameter of just 2.50 mm, which is equivalent to the outer diameter of a standard 6F sheath introducer (Fig. 2). This inner diameter provides the option to position a large variety of biotomes in the LV. For the majority of patients, we used this 7.5F EauCath sheathless guide in combination with a 5.4F bioptome (Maslanka Cardiobioptome, Maslanka, Tuttlingen Germany) with an overall outer diameter of 1.8 mm for all (Fig. 3) except the first three patients, in whom we used an 8.5F EauCath sheathless guide in combination with the institutional standard Meiners Bioptome (Meiners Medizintechnik GmbH, Monheim, Germany).

Fig. 2
figure 2

Comparison of the outer diameter of the Asahi EauCath® Sheathless Guiding Catheter with a standard sheath introducer. Note that the inner diameter of the EauCath® Sheathless Guiding Catheter compares to a larger standard sheath introducer, see text for details

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Fig. 3
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Comparison of the inner diameter of the EauCath® Sheathless Guiding Catheter with the outer diameter of 5.4F Maslanka Cardiac Bioptome

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An MP2 curve was used in the first case, whereas for the following procedures the MP1 was chosen, since it turned out to be the more suitable curve. For all types, the guiding catheter was inserted over a 0.035″ angiographic wire. The sheathless EauCath catheters require a dilator during insertion to reduce the gap between the guide wire and the catheter, since it requires a certain degree of stiffness to insert the catheter into the body where the dilator takes an active role. Given the rather sharp end of the dilator, unlike for standard transradial procedures, the guide was continuously advanced under fluoroscopic control until the tip of the inlet reached the ascending aorta. The inlet was removed over a regular guide wire and replaced by a 6F standard pigtail catheter for crossing of the aortic valve. Once in the LV cavity, the pigtail catheter was removed and the position of the guide pointing towards the free LV was confirmed in two planes (RAO 35° and LAO 60°). A standard Y-shaped hemostasis valve was connected to the guide and the system was thoroughly flushed with saline after connection to the standard institutional angiography manifold (Fig. 4).

Fig. 4
figure 4

a Demonstrates the introduction of the Sheathless Guiding Catheter into the right radial artery. An overview of the typical setup for transradial EMB, including the guide, the Y-shaped hemostatic valve, the angiography manifold, as well as the bioptome is provided in b. c Depicts the removal of the guide with the inflated standard compression device already in place. After removal of the guide instant hemostasis is achieved, as shown in d. See text for additional details

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The guide wire was then replaced by the bioptome. Under subsequent fluoroscopic control up to ten biopsy samples were obtained from different locations of the LV. During the procedure, air aspiration was carefully avoided by repetitive back bleeding and manual flushing. Finally, the initial angiographic wire replaced the bioptome, and with the guide still in place a standard compression device (TR-Band®, TERUMO) was placed over the access site and inflated with 12 ml air. The guide could then easily be removed while instant hemostasis was achieved. Patients routinely received immediate bedside echocardiography to rule out pericardial effusion. Radial patency was assured by duplex sonography 24 h after the procedure.

Data analysis and statistics

Safety and efficacy parameters were: (1) procedural success, (2) quality of biopsy samples as assessed by participating pathologists, (3) radiation exposure, (4) procedural time, (5) time to ambulation, (6) access site vessel patency, and (7) relevant access site complications (defined as: false aneurysm, AV-fistula, drop in hemoglobin of more than two points without pericardial effusion or other overt bleeding requiring action, indication for bed rest due to the procedure).

Since the objectives of this safety and efficacy evaluation are descriptive in nature, no formal hypothesis testing was done. Absolute numbers and percentages were computed to describe the patient population. Medians (with quartiles) or means (with standard deviation) were computed as appropriate. All statistical analyses were performed using the SAS© statistical package, version 9.2 (SAS, Cary, North Carolina).

Results

Patient population

Mean age was 56 years and 31 % of patients where female. The mean BMI of 29 kg/m2 reflects relevant over weight in our patient cohort. Most patients had moderately or severely impaired LV-EF (median 34 %). At the time of the procedure, 40 % of patients where on anti-platelet therapy, and 26 % where treated with some form of oral anticoagulation. Whereas anti-platelet medication was continued, oral anticoagulation was stopped and the INR had to be <2.0 before the transradial invasive procedure. The median INR was 1.15, ranging from 1.0 to 1.75, with a median platelet count of 215 GIGA/l, ranging from 108 to 436 GIGA/l. Additional patient characteristics can be viewed in Table 1.

Procedural characteristics, safety and efficacy

Depending on the clinical indication, the transradial invasive evaluation encompassed the whole spectrum from EMB as a standalone procedure, combined left/right heart catheterization, or even PCI following FFR. To rule out functional coronary or micro vascular disease as an underlying cause for LV dysfunction, an additional intracoronary acetylcholine test was performed in 13 individuals.

In one case, there was a need to cross over to femoral access due to irreversible spasm of the right radial artery after administration of local anesthesia, while no further case of radial spasm was observed. Thus, the success rate of EMB via transradial access was 98 % (41 of 42) in our population. Table 2 provides a detailed overview of the different procedures performed during the invasive evaluation, as well as the final diagnosis obtained by EMB.

Table 2 Overview of procedures performed and final diagnosis
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The median duration of the invasive evaluation was 44 min (range 20–86 min), including all procedures performed in one individual. The mean amount of contrast media used was 120 ml per patient, ranging from 20 to 350 ml, also depending on the procedures performed (Table 2). The number of biopsy samples harvested depended on operators’ discretion but was not less than six in any patient and 8.4 samples were obtained per patient in average. All biopsy samples harvested via transradial access where graded as good or excellent quality by the pathologists involved. We did not obtain any biopsy sample that was not diagnostic. No patient had access site-, or any other complications as specified before. Immediate post-procedural ambulation could be achieved in all patients independent of the procedures performed, as for no patient any bed rest was assumed necessary.

Overall mean fluoroscopy time was 7.9 min ranging from 2 to 26 min, depending on the procedures performed (Table 3; Fig. 5). The median dose area product was 1867 cGy × cm2, with a median skin dose of 607 mGy. All patients had patent radial arteries 24 h after removal of the guide confirmed by duplex sonography.

Table 3 Efficacy and safety parameters
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Fig. 5
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Detailed distribution and respective fluoroscopy times for all different combinations of invasive procedures performed in this study. All values expressed in minutes as median and quartiles. Note the dependence of the fluoroscopy time on the invasive procedures performed in the individual patient

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Discussion

The present study demonstrates safety and efficacy of a systematic transradial approach for left ventricular EMB. This is of clinical importance since the new transradial technique may overcome limitations of the commonly used femoral approach, such as bleeding form the access site due to the need for large diameter sheaths, or strict post-procedural immobilization. Therefore, LV-EMB via transradial access may be the new interventional technique of choice, improving the safety of EMB [7].

Patient population

Age, gender, and body mass index distribution in our patient population (Table 1) was in line with many other study populations presenting for the work-up of heart failure in the western world [14, 15]. This also holds true for the mean left ventricular function and other functional parameters [15, 16] (Table 1). Oral anticoagulation, which is frequently indicated in heart failure patients, was stopped before invasive evaluation. However, all invasive procedures were performed up to an INR of 2.0, making the management of patients on oral anticoagulation easier, nicely underscoring the advantages of the transradial access [8, 9, 17].

Procedural characteristics, safety and efficacy

Procedures encompassed the whole spectrum ranging from EMB as a standalone procedure, or combined left/right heart catheterization to PCI following FFR measurement, reflecting the potential of the transradial approach (Fig. 5). Consequently, transradial access may be regarded as an interventional “one stop shop” technique.

The success rate in our population was 98 % (41 of 42). In one patient, we had to cross over to femoral access due to irreversible spasm of the right radial artery after administration of local anesthesia. Despite the fact that the incidence of radial spasm greatly varies in literature [18], our cross over rate nicely matches other reports of transradial interventions [17]. Importantly, the use of the sheathless guiding catheter along with a matching bioptome did not result in any radial spasm in all 41 patients undergoing EMB. The procedural time and the amount of contrast agent used (Table 2) depended on the procedures performed in each individual patient, and were very acceptable compared to other datasets [19].

According to our pathologists, the quality of the biopsy specimens was good or excellent (Table 3), allowing complete work-up of EMB from all patients regarding histology, immunohistology and molecular pathology (infections). Despite a mean BMI of 29 kg/m2, a maximum INR of up to 1.75, and 40 % of patients being on anti-platelet medication, we did not experience any bleeding or other access site complication, also underscoring the advantages of the transradial approach. After exclusion of pericardial effusion by bedside echocardiography, all patients could immediately be mobilized, which may significantly reduce the length of hospital stay required, possibly offering a considerable economic benefit [20]. Fluoroscopy time and radiation dose (Table 3) were also dependent on the procedures performed, and compare well with other interventional datasets [19, 21].

Another frequent concern raised with regard to transradial procedures is the access vessel patency, potentially limiting multiple accesses [22]. However, in our sample, all access vessels were confirmed patent by duplex sonography 24 h after removal of the guide.

Clinical implications

A procedure combining the advantages of LV-EMB [6] with the benefits of transradial access [8, 9, 17] seems very desirable for the clinical routine. Consequently, the present study may serve as a blueprint for operators willing to perform transradial EMB with its unquestionable advantages. However, in the current study, we did not have a randomized control group allowing direct comparison of procedural parameters and results to the standard femoral approach. In addition, there is an obvious heterogeneity among the procedures performed in our population, reflecting the needs of a real world clinical routine setting. A prospective randomized trial could further investigate the advantages of the transradial approach for LV-EMB.

Conclusion

The present study demonstrates safety and efficacy of a systematic transradial access for left ventricular EMB using a highly hydrophilic sheathless guiding catheter. This is of clinical importance since with transradial biopsy bleeding is less likely than by the transfemoral approach and immediate patient ambulation can be achieved.