Access to side branches with a sharply angulated origin: usefulness of a specific wire for chronic occlusions

INTRODUCTION

Currently, distal radial access (DRA) in the anatomical snuffbox for both noncoronary and coronary procedures is gaining popularity. Since its introduction by Babunashvili et al.,1 in 2011, several observational studies have validated the feasibility and safety of DRA,2-4 comparing it with conventional transradial access (TRA). DRA has shown advantages such as a lower incidence of radial artery occlusion (RAO) and shorter hemostasis time, with minimal access-related complications.5,6 The usefulness of ultrasound to guide DRA and evaluate access-related complications has also been described.7,8 Recent randomized trials comparing DRA with TRA have reported conflicting results regarding RAO incidence, crossover rates, and access times.9-11 Nevertheless, meta-analyses consistently support the benefits of DRA, albeit with a higher crossover rate.12-13 One of the limitations of most studies on DRA is the restricted inclusion of patients in emergent situations or complex percutaneous coronary interventions (PCI), such as ST-segment elevation myocardial infarction (STEMI); therefore, the feasibility of the approach in this context is somewhat scarce.2,9-11,14 Despite current evidence, the use of DRA as the default access for coronary procedures is still not widely implemented in most centers. Hence, this prospective single-center cohort aimed to present the experience of our first 1000 DRA in patients undergoing coronary procedures in any clinical settings.

METHODS

Population and study design

The Distal Radial Access for Diagnostic and Interventional Coronary Procedures in an all-comer population (DISTAL) registry is a prospective observational investigation aiming to assess the performance of DRA and compare clinical and procedural characteristics in a diverse population undergoing coronary procedures. This interim analysis presents our initial experience with DRA conducted at a single center. All DRA procedures performed by 4 experienced operators, previously proficient in TRA, were included in the study from August 2020 to November 2023.

This study was approved by the Ethics Committee of our institution (CEIC-2804) and was conducted following the principles of the Declaration of Helsinki. All patients gave their informed written consent before the procedure.

Inclusion and exclusion criteria

The study included patients aged 18 years and older undergoing diagnostic or therapeutic coronary procedures using DRA in any clinical setting. Patients with an unsuitable distal radial artery (DRart) assessed by ultrasound (non-permeable or diameter <1 .8 mm) were excluded, as were patients with no palpable pulse of DRart with such unsuitability characteristics. Additional exclusion criteria encompassed participation in other clinical trials, known allergy to iodinated contrast, inability to provide informed consent, and women of childbearing age without a negative pregnancy test. While the Barbeau test was recommended, it was not mandatory for inclusion.15

Endpoints

The primary endpoint was the success of DRA and the main secondary endpoint was the success of the coronary procedure. Other secondary endpoints included DRA procedure time, total procedure duration, the incidence of radial artery spasm, exposure to ionizing radiation, patient comfort levels, hemostasis time, access-related complications, and the impact of ultrasound guidance on DRA performance. Detailed definitions of these endpoints are provided in the supplementary data.

Distal radial access technique

The DRA technique has been previously described,2,4,16-18 and is explained in detail in the supplementary data. Key aspects of interest included patient selection, the decision to use ultrasound-guided puncture19 (figure 1) vs blind with palpation puncture at the discretion of the operator, patient positioning for right (r) or left (l) DRA, the puncture technique itself, and the hemostasis procedure (figure 2).

Figure 1. A: markers for ultrasound positioning in the anatomical snuffbox. B: patency of the distal radial artery (DRart) confirmed by color Doppler ultrasound. C-D: course of DRart between the metacarpal bones. E-F: recommended puncture sites of the DRart on a surface bone. IM, index metacarpal; SB, scaphoid bone; TB, trapezium bone; TM, thumb metacarpal.

Figure 2. Distal radial access (DRA) technique. Position of the hand for A) right DRA and B) left DRA. C: ultrasound-guided DRA technique. D: blind with palpation DRA puncture. E: final position of the introducer sheaths on the right and left DRA. F: hemostasis devices in DRA.

Statistical analysis

Sample size and statistical power calculations were performed using the GRANMO calculator.20 A sample size of 1000 procedures was determined to provide a statistical power greater than 99% to detect a difference of 3% or more in the proportion of DRA success (primary endpoint) at our center, assuming an alpha risk of 1%. This calculation was based on a reference proportion from previous medical literature estimated around 95%.11,18,21

Categorical variables are presented as counts (percentages), while continuous variables were assessed for normal distribution using the Kolmogorov-Smirnov test. Normally distributed variables are expressed as mean (standard deviation), and nonnormally distributed variables as median [interquartile range].

To evaluate the impact of the learning curve, comparisons were made among quartiles of the study period for variables including access failure, DRA time, total procedure time, and access-related complications. Analysis of variance or the Kruskal-Wallis test was used depending on the normality of the variable. Logistic regression analysis (logit command) was used with the first quartile as the reference to compare percentages among quartiles.

Statistical analyses were conducted using SPSS Statistics 20.0 software (IBM, United States) and STATA 12 (StataCorp, College Station, United States). A p-value < 0.05 was considered statistically significant for all tests.

RESULTS

From August 2020 to November 2023, a total of 1000 DRA procedures (943 patients) were performed. Table 1 shows the patients’ baseline clinical characteristics. The mean age was 68 years, and 29% of the patients were women. A total of 47% of the procedures were performed on an outpatient basis. In 35% of cases, the indication was acute coronary syndrome (13% STEMI).

Table 1. Baseline clinical characteristics

Clinical characteristics	n = 1000
Age, (years), mean (SD)	68.1 (11.7)
Female, n (%)	289 (28.9)
Weight, (kg), mean (SD)	78.0 (14.8)
Height, (cm), mean (SD)	167.9 (8.1)
Body mass index, (kg/m2), mean (SD)	28.0 (4.5)
Hypertension, n (%)	735 (73.5)
Dyslipidemia, n (%)	578 (57.8)
Diabetes mellitus, n (%)	353 (35.3)
Current smoker, n (%)	246 (24.6)
Family history of premature coronary heart disease, n (%)	54 (5.4)
Previous peripheral artery disease, n (%)	50 (0.5)
Previous stroke, n (%)	41 (4.1)
Previous heart failure, n (%)	252 (25.2)
GFR (mL/minute/1.73m2), mean (SD)	72.4 (20.0)
Dialysis, n (%)	27 (2.7)
Left ventricular ejection fraction, mean (SD)	52.6 (16.2)
Atrial fibrillation, n (%)	170 (17.0)
OAC
Acenocoumarin, n (%)	170 (17.0)
Direct OAC, n (%)	81 (8.1)
Previous CAG, n (%)	251 (25.1)
Previous CABG, n (%)	43 (4.3)
Previous PCI, n (%)	218 (21.8)
Previous ischemic heart disease
Previous STEMI, n (%)	133 (13.3)
Previous NSTEMI, n (%)	69 (6.9)
Previous CCS, n (%)	53 (5.3)
CAG indication
Chronic coronary syndrome, n (%)	207 (20.7)
STEMI, n (%)	128 (12.8)
NSTEMI, n (%)	224 (22.4)
Staged PCI, n (%)	60 (6.0)
Diagnostic, n (%)	381 (38.1)
Preoperative CAG in patients with VHD, n (%)	183 (18.3)
Dilated cardiomyopathy, n (%)	158 (15.8)
Ventricular tachycardia, n (%)	24 (2.4)
Others, n (%)	16 (1.6)
Outpatient coronary arteriography, n (%)	470 (47)
CABG, coronary artery bypass grafting; CAG, coronary angiography; CCS, chronic coronary syndrome; GFR, glomerular filtration rate; NSTEMI, non−ST-segment elevation myocardial infarction; OAC, oral anticoagulation; PCI, percutaneous coronary intervention; STEMI, ST-segment elevation myocardial infarction; VHD, valvular heart disease. Data are expressed as No. (%) or mean ± standard deviation.

Table 2 presents the characteristics of the radial artery and the DRA procedure. High rates of preprocedure ultrasound evaluation and ultrasound-guided technique for DRA were noted (83% and 85%, respectively). Notably, the percentage of coronary procedures showing insufficient catheter length due to DRA was low (3.7%).

Table 2. Characteristics of the DRA procedure

Procedure characteristics	n = 1000
Preprocedure characteristics
Arterial pulse strength scale
Absent, n (%)	12 (1.2)
Weak, n (%)	167 (16.7)
Normal, n (%)	652 (65.2)
Strong, n (%)	169 (16.9)
Radial artery preprocedure ultrasound evaluation, n (%)	830 (83.0)
Arterial tortuosity
Radial, n (%)	23 (2.3)
Subclavian, n (%)	62 (6.2)
Calcified radial artery, n (%)	26 (2.6)
Distal radial artery size, mm (SD)	2.3 (0.3)
Proximal radial artery size, mm (SD)	2.5 (0.4)
Depth of the distal radial artery, mm (SD)	3.8 (1.0)
DRA technique
CAG by the same DRA, n (%)	57 (5.7)
Ultrasound-guided access, n (%)	848 (84.8)
DRA side
Right DRA, n (%)	627 (62.7)
Left DRA, n (%)	373 (37.3)
Introducer size
5 French, n (%)	256 (25.6)
6 French, n (%)	744 (74.4)
Introducer sheath type
Prelude Ideal (Merit Medical) Introducer Kit, n (%)	950 (95.0)
Radifocus Introducer II Kit A (Terumo Corporation), n (%)	50 (5.0)
Short length of the radial catheter	37 (3.7)
Postprocedure arterial patency evaluation, n (%)	907 (90.7)
Postprocedure puncture site bleeding, n (%)	55 (5.5)
CAG, coronary angiography; DRA, distal radial access. Data are expressed as No. (%) or mean ± standard deviation.

Table 3 summarizes the characteristics of coronary procedures, including the extent of coronary artery disease, types of procedures, and features of patients who underwent PCI. In general, 64% of the procedures were only diagnostic, while 36% included PCI.

Table 3. Characteristics of the coronary procedure

Procedure characteristics	n = 1000
Coronary disease extent
One vessel, n (%)	285 (28.5)
Two vessels, n (%)	174 (17.4)
Three vessels, n (%)	176 (17.6)
LMCAD, n (%)	55 (5.5)
Coronary bypass graft, n (%)	27 (2.7)
Characteristics of the coronary procedure
Type of coronary procedures
Diagnostic, n (%)	644 (64.4)
PCI, n (%)	356 (35.6)
Ambulatory PCI, n (%)	90 (9.0)
PCI culprit lesion
LMCAD, n (%)	9 (0.9)
Left anterior descending artery, n (%)	164 (16.4)
Circumflex coronary artery, n (%)	95 (9.5)
Right coronary artery, n (%)	100 (10.0)
Coronary bypass graft	2 (0.2)
Specific techniques
Wire-based intracoronary physiological assessment, n (%)	57 (5.7)
Optical coherence tomography, n (%)	21 (2.1)
Intravascular ultrasound, n (%)	30 (3.0)
Guide catheter extension system, n (%)	15 (1.5)
Rotational atherectomy, n (%)	16 (1.6)
Cutting balloon, n (%)	34 (3.4)
Intracoronary lithotripsy, n (%)	8 (8.0)
Thrombus aspiration, n (%)	81 (8.1)
Intracoronary perfusion catheter, n (%)	7 (0.7)
Special PCI procedures
Complex bifurcation, n (%)	60 (6.0)
Chronic total occlusion, n (%)	16 (1.6)
Volume of contrast, (mL), mean (SD)	85.0 (53.1)
Heparin dose, (IU), median [IQR]	5000 (3000-8500)
LMCAD, left main coronary artery disease; PCI, percutaneous coronary intervention.

Table 4 depicts the clinical endpoints. The DRA success rate was 97.4% and the coronary procedure success rate was 96.9%. The median access time was 40 (interquartile range [IQR], 30-60) seconds, and 4% of patients experienced radial artery spasm. The overall rate of access-related complications was low (2.9%).

Table 4. Clinical endpoints

Clinical endpoints	n = 1000
Primary endpoint
DRA success, n (%)	974 (97.4)
Coronary procedure success by DRA, n (%)	969 (96.9)
Secondary endpoints
Access time, (sec), median [IQR]	40 (30-60)
Procedure time, (min), median [IQR]	29.0 [17.3-45.0]
Radial artery spasm, n (%)	44 (4.4)
DAP, (Gy.m2), median [IQR]	32.7 [19.2-63.0]
Fluoroscopy time (min), median [IQR]	4.6 [2.5-10.0]
VAS patient comfort for access, mean (SD)	2.2 (0.6)
VAS patient comfort for hemostasis, mean (SD)	2.1 (0.4)
Hemostasis time, (hour), mean, (SD)	2.9 (1.1)
Access-related complications (all), n (%)	29 (2.9)
Radial artery occlusion, n (%)	10 (1.0)
Hematoma, n (%)
Type I-a, n (%)	11 (1.1)
Type I-b, n (%)	1 (0.1)
Type II, n (%)	1 (0.1)
Type III, n (%)	1 (0.1)
Type IV, n (%)	0 (0)
Radial pseudoaneurysm, n (%)	0 (0)
Radial dissection, n (%)	5 (0.5)
Arteriovenous fistula, n (%)	0 (0)
DAP, dose-area product; DRA, distal radial access; VAS, visual analog scale. Data are expressed as No. (%), mean ± standard deviation, or median [interquartile range].

Combined preprocedure ultrasound evaluation and ultrasound-guided puncture were performed in 82.8% of cases, with successful DRA achieved in 97.7% compared with 95.9% in those who did not undergo ultrasound guidance (P = .183). Based on the strength of the arterial pulse—absent, weak, normal, and strong—ultrasound-guided puncture was performed in 100%, 91%, 89.7%, and 45.5% of cases, respectively. Access time was longer with ultrasound-guided puncture than with nonultrasound-guided puncture (40 s [30-70] vs 35 s [30-45]; P < .001). The success of DRA in relation to the use of ultrasound-guided technique among all strengths of arterial pulse is detailed in table 1 of the supplementary data.

Arterial patency after removal of the hemostatic device was assessed in 907 patients (90.7%), revealing RAO in only 1% (n = 10).

In the quartile analysis, a shift in the selection of DRA side was observed, with lDRA initially more commonly used, shifting to rDRA as the preferred access in later quartiles (figure 3A). DRA failure rates were low in all quartiles but decreased significantly from the third quartile onwards (figure 3B). Access time decreased significantly from the second quartile onwards and remained stable thereafter (figure 3C). However, no significant differences were found in total procedure duration between quartiles (figure 3D).

Figure 3. Stratified analysis by quartiles of patients over the study period. A: use of left vs right distal radial access (DRA). B: DRA access failure rate by quartile. C: DRA access time in seconds. D: total procedural time in minutes.

DISCUSSION

Using data from a large prospective registry of patients who underwent DRA for coronary procedures, with high use of ultrasound-guided techniques, our study showed that DRA achieves high rates of access and procedural success, coupled with a low incidence of access-related complications in an all-comer population.

The usefulness of ultrasound in the distal radial access technique

Understanding the anatomy of the anatomical snuffbox is crucial for successful DRA, and ultrasound serves as a valuable tool in achieving this, offering demonstrated advantages.5,16,17,22 In our study, preprocedure ultrasound evaluation and ultrasound-guided DRA techniques were used in most patients. In addition to assessing arterial diameters and evaluating calcification and tortuosity, ultrasound enabled us to exclude patients with unsuitable distal radial arteries. Overall, we found no significant differences between ultrasound-guided and nonultrasound-guided DRA, although the former was associated with longer access times. However, the role of ultrasound is particularly noteworthy in cases of weak or absent arterial pulses, which are often underrepresented in prior studies. The presence of a suboptimal arterial pulse can stem from various factors, including small DRart, hypotension, collateral blood supply, or depth of DRart.11 In our study, most patients with weak pulses underwent ultrasound-guided puncture, with a favorable trend toward successful access in those who did. However, in patients with normal to strong pulses, no differences in DRA success were found, and even prolongation of access time was observed with its use. Therefore, in this type of pulse, an ultrasound-guided puncture is probably not necessary.

Feasibility, safety, and technical issues in distal radial access

This study corroborates the previously reported advantages of DRA,3,9,10,12,13,18 such as a low rate of RAO, acceptable access time, short hemostasis time, and adequate patient comfort.

Furthermore, the absence of an increased risk of hand dysfunction after DRA has been demonstrated,23 even compared with TRA at 12 months of follow-up, documented by Al-Azizi et al.24 Here, we focus on controversial issues that may have hampered wider adoption of this technique, and our results may provide additional support for DRA.

High success rates of DRA in coronary procedures have been reported in numerous studies.2-4,17,18,25 In addition, recent clinical trials and meta-analyzes describe a higher crossover rate compared with TRA.9-13

In contrast to our results, trials comparing DRA with TRA have reported lower access success and longer puncture times.9-11 Conversely, our study demonstrates remarkably high success rates for DRA and coronary procedures, as well as shorter access time, consistent with registries in which DRA is the default approach among experienced operators, as shown by the largest registries published to date, the DISTRACTION and KODRA studies.2-4,18,21

The KODRA trial included 4977 DRA procedures from a Korean registry.21 The authors reported a DRA success rate of 94.4%, with a crossover rate of 6.7%. In contrast to our work, the use of ultrasound-guided puncture in KODRA was low (6.4%). Additionally, the authors found predictors of DRA failure, such as the presence of a weak pulse and limited operator experience (less than 100 cases).

The equivalence of rDRA and lDRA has previously been demonstrated, and contemporary studies use mainly rDRA.9-11,17 As in the first registries, which suggested a potential advantage of lDRA, we started our experience with lDRA but, based on operator comfort and preference, the use of the rDRA increased over time.

Although the feasibility and benefits of DRA over TRA in STEMI have been observed, the literature on the topic remains scarce.2,9-11 In our registry, all attempted DRA procedures in patients with STEMI were successful. However, the first DRA in STEMI was performed after the operators had surpassed the learning curve for the technique (up to case 320). Similarly, the use of DRA for complex PCI has been previously described.22,26,27 In our cohort, all complex PCI procedures were performed without crossover.

The puncture site in DRA, situated 5 cm distal to TRA, may lead to an inadequate catheter length in specific contexts (such as tall patients, dilated aorta, subclavian artery tortuosity, and the need for retrograde access to PCI for chronic total occlusions).28 We found a low incidence of short catheter length during DRA procedures, with only 1 crossover due to severe tortuosity of the subclavian artery.

DRA-related complications have been consistently reported to be low.2,9-11,18 Similarly, we found a very low rate of complications, the most common being type I-a hematoma. In our study, the incidence of in-hospital RAO was 1%.

The number of DRA procedures to overcome the learning curve and maintain a success rate above 94% is around 150 to 200.2,8 However, in our early experience, we achieved this percentage after the first 20 cases per operator.17 In this study, operators navigated the learning curve in the first quartile; however, success significantly improved to more than 99% in the last 2 quartiles, probably because DRA became the default access for coronary procedures among operators.

Limitations

First, this study was an interim analysis of the leading participating site and coordinator of the DISTAL registry (NTC06165406), conducted because substantial enrollment from other sites was lacking. Although the data cannot be fully extrapolated to other centers, recalculation of the sample size was considered sufficient to evaluate the results.

Second, patient enrollment was not consecutive because the decision to use DRA was at the operators’ discretion. Only one-third of coronary procedures during the study period used this approach. However, we included all patients in whom operators intended to use DRA in any clinical setting were included, with only 21 patients excluded due to DRart ≤1.8mm. Third, this was a descriptive cohort of DRA, without a comparison control group. Fourth, the scale used to assess the arterial pulse is subjective. However, this scale is widely used in routine clinical practice and has been used in multiple DRA studies. Finally, radial artery patency was not evaluated in 9.7% of the patients before discharge, and no evaluation was conducted at 1 month; therefore, the in-hospital rate of radial artery occlusion may be underestimated and no mid-term data are available on the patency of the DRart.

CONCLUSIONS

This study shows the safety and feasibility of DRA primarily guided by ultrasound for coronary procedures in an all-comer population, with high rates of both access and procedural success, in addition to a very low rate of access-related complications.

FUNDING

None declared.

ETHICAL CONSIDERATIONS

This study was approved by the Ethics Committee of our institution (CEIC-2804) and was conducted following the principles of the Declaration of Helsinki. All patients gave their informed written consent before the procedure.

STATEMENT ON THE USE OF ARTIFICIAL INTELLIGENCE

Not used.

AUTHORS’ CONTRIBUTIONS

K. Rivera and D. Fernández-Rodríguez conceived and designed the study. K. Rivera, D. Fernández-Rodríguez, M. García-Guimarães, J. Casanova-Sandoval, and J. L. Ferreiro analyzed data, and drafted the manuscript. All authors contributed to the treatment of patients, data acquisition and mining, and review and approval of the final version of the manuscript.

CONFLICTS OF INTEREST

J. L. Ferreiro reports a) honoraria for lectures from Eli Lilly Co, Daiichi Sankyio, Inc, AstraZeneca, Pfizer, Abbott, Boehringer Ingelheim, Bistol-Myers Squibb, Rovi, Terumo and Ferrer; b) consulting fees from AstraZeneca, Eli Lilly Co, Ferrer, Boston Scientific, Pfizer, Boehringer Ingelheim, Daiichi Sankyo, Inc, Bristol-Myers Squibb and Biotronik; c) research grants from AstraZeneca. The remaining authors have no conflicts of interest to declare.

REFERENCES

INTRODUCTION

Patients with coronary in-stent restenosis (ISR) represent a clinical challenge.1 Evidence indicates that these patients are at increased risk of recurrent symptoms, myocardial infarction, and repeated coronary revascularizations.2 The use of drug-eluting balloons (DEB) is a novel alternative therapeutic strategy in patients with ISR.1,3,4 The effect of DEBs in coronary angioplasty is based on the rapid and uniform transfer of antiproliferative drugs into the vessel wall using a single balloon through a lipophilic matrix without the need for permanent implants.5

Over time, new DEB technologies are developed and launched onto the market. The Essential Pro (iVascular, Spain) is a paclitaxel-eluting balloon catheter with advancements to enhance catheter pushability and drug delivery. We believe it is essential to report outcomes from real-world settings. In this study, we report our findings on the safety and efficacy of this new DEB in patients with ISR.

METHODS

Design and population

This prospective, single-center study included a cohort of consecutive patients undergoing DEB angioplasty with the Essential Pro. The center treating these patients performs more than 1500 percutaneous coronary interventions per year. The 2 inclusion criteria for this analysis were: a) use of an Essential Pro DEB and b) its application for ISR treatment. ISR was defined as stenosis more than 50% within the stented segment, and treatment was indicated according to the treating physician’s judgment.6 The use of the Essential Pro DEB was prioritized during the study period to treat all eligible patients for DEB angioplasty, while other DEB devices were rarely used due to inventory constraints. There were no exclusion criteria. Patients may have undergone stent coronary angioplasty of other lesions in the same or a different setting.

Drug-eluting balloon characteristics

The Essential Pro is a paclitaxel-eluting balloon with a uniform 3 μg/mm2 eluting formulation, consisting of paclitaxel (80%) and a biocompatible amphiphilic excipient (20%).7 The balloon incorporates the proprietary TransferTech technology (iVascular, Spain), which is based on the ultrasonic deposition of nanodrops, followed by a dry-off process, resulting in a homogeneous microcrystalline drug coating. This allows more uniform and complete treatment of the vessel with the antiproliferative drug. The microcrystalline structure, coupled with the lipophilic nature of both paclitaxel and the excipient, facilitates drug transfer within 45 to 60 seconds. The Essential Pro balloon has been designed with a smooth transition and a very low tip profile of 0.016 inches, enhancing flexibility, trackability, and device crossability. The balloon is compatible with 5-Fr sheaths in all available diameters.

Procedures

All procedures and decisions in this study reflect real-world clinical practice. Therefore, clinical indications, the use and selection of DEBs, procedural steps, and medical treatments were decided by treating physicians without following any specific guidelines. All coronary angiograms performed during follow-up were part of routine clinical practice and were assessed by our research team when available. Baseline and follow-up data were collected in a single anonymized dedicated database. Procedural aspects, as well as both baseline and follow-up angiograms, were independently evaluated by 3 different interventional cardiologists. Physicians were trained to consult senior staff if they had doubts when assessing angiograms or clinical records. Follow-up was conducted using clinical records, and patients with no on-site clinical visits during follow-up were contacted by telephone following standard clinical practice in our institution. This study was approved by our local institutional review board and patients provided consent for the use of their anonymized information for research purposes before inclusion. This was an investigator-initiated study with no sponsoring or funding.

Outcome definitions

Device delivery was defined as successful DEB insufflation in the affected coronary segment. Procedural, angiographic, and other standard outcomes were defined according to the Second Academic Research Consortium criteria.8 Cardiovascular mortality was defined as any death without a clear noncardiovascular cause. Acute myocardial infarction was defined as any myocardial infarction meeting the fourth version of the Universal Myocardial Infarction Criteria.9 Target lesion revascularization (TLR) was defined as any revascularization within or 5 mm beyond the treated segment.8 Target vessel revascularization (TVR) was defined as revascularization of the index treated vessel.8 Coronary-related hospitalization was defined as a new hospitalization in which a coronary origin was suspected as the main reason for admission. The 3 main efficacy outcomes were myocardial infarction, TLR, and TVR.

Statistical analysis

Categorical variables are presented as percentages, and continuous variables as mean standard deviation (SD) when appropriate. Since the same patient may receive more than 1 DEB (for the same or different territory), the denominator for balloon-specific variables was based on the total DEBs used (such as treated vessel, vessel diameter, DEB diameter, and length), while the denominator of patient-level variables (such as age, sex, or clinical outcomes) was each single individual. Clinical outcomes during follow-up are presented at 30 days, 1 year, and total follow-up. The Kaplan-Meier method was used for estimating both the total follow-up risk and generating survival curves. Data were analyzed using IBM SPSS Statistics 25.

RESULTS

From December 2020 to June 2023, 290 patients with 352 coronary lesions were treated with DEB. Among them, 160 patients (206 lesions) underwent DEB angioplasty due to ISR. Out of the 160 patients receiving DEB for ISR, 46 patients (29%) received more than 1 DEB angioplasty for ISR, either during the same procedure or staged to a different lesion.

The patients’ baseline characteristics are summarized in table 1. The mean age was 71.4 ± 14.9 years, 15.5% were women, and 35.5% had diabetes. Clinical presentation was stable angina in 29.7%, unstable angina in 30.5%, non–ST-segment elevation myocardial infarction in 9.9%, ST-segment elevation myocardial infarction in 12.9%, and 16.7% were asymptomatic.

 

Table 1. Baseline characteristics

Patient characteristics
Age, y	71.4 (14.9)
Sex women	20 (15.5)
BMI, kg/m2	29.2 (10.5)
Hypertension	115 (87.7)
Active smoking	8 (6.1)
Diabetes mellitus	46 (35.3)
Previous MI	67 (51.5)
Previous CABG	26 (20)
Reduced LVEF (< 30%)	10 (7.6)
Laboratory parameters
Hemoglobin, g/dL	13.9 (1.5)
GFR, mL/min/1.73 m2	82.9 (25.4)
Active medication
Aspirin	110 (84.6)
Clopidogrel	75 (57.6)
Ticagrelor	3 (2.3)
Prasugrel	2 (1.5)
Anticoagulation	20 (15.2)
Clinical presentation
Silent ischemia	22 (16.7)
Stable angina	39 (29.7)
Unstable angina	40 (30.5)
NSTEMI	13 (9.9)
STEMI	17 (12.9)
BMI, body mass index; CABG, coronary artery bypass grafting; GFR, glomerular filtration rate; LVEF, left ventricular ejection fraction; MI, myocardial infarction; NSTEMI, non–ST-segment elevation myocardial infarction; STEMI, ST-segment elevation myocardial infarction. Data are expressed as No. (%).

 

Procedural characteristics are detailed in table 2. The most commonly treated vessel was the left anterior descending artery (48.7%), followed by the left circumflex (30.7%), and the right coronary artery (17%). Bifurcation was present in 10.7%. Lesion preparation was performed in 98.2% of cases (80% with a noncompliant balloon). Intracoronary imaging was used in 24% of patients. None of the patients underwent rotational atherectomy, and 2.4% underwent balloon lithotripsy before DEB delivery. The mean vessel diameter was 3.1 ± 0.65 mm. The mean DEB diameter was 3.1 ± 0.6 mm, and the mean length was 23.1 ± 6.8 mm. Device delivery was successful in 100% of cases (figure 1). The final angiographic assessment revealed a final dissection in 1.4%, Thrombolysis in Myocardial Infarction flow less than 3 in 1.5%, and residual stenosis more than 30% in 3.4%. Bail-out stenting was needed in 4.8%.

 

Table 2. Characteristics of the treated lesion

Treated vessel
LAD	100 (48.7)
LCx	63 (30.7)
Right coronary artery	35 (17)
Left main coronary artery	5 (2.4)
Graft	2 (0.9)
Anatomical characteristics
Bifurcation lesion	22 (10.7)
Vessel diameter, mm	3.1 (0.65)
Procedural characteristics
IVUS-guided PCI	51 (24)
Lesion predilatation	202 (98)
Predilatation with NC balloon	165 (80)
Intravascular lithotripsy	5 (2.4)
DEB diameter, mm	3.1 (0.6)
DEB length, mm	23.1 (6.8)
Result after DEB PCI
Vessel dissection	3 (1.4)
TIMI flow 3	203 (98.5)
Residual stenosis > 30%	194 (3.4)
Bail-out stenting	10 (4.8)
DEB, drug-eluting balloon; IVUS, intravascular ultrasound; LAD, left anterior descending artery; LCx, left circumflex artery; NC, noncompliant; PCI, percutaneous coronary intervention; RCA, right coronary artery; TIMI, Thrombolysis in Myocardial Infarction. Data are expressed as No. (%).

Figure 1. Central illustration. Main findings on the safety and efficacy of the Essential Pro drug-eluting balloon in patients with in-stent restenosis. Kaplan-Meier shows freedom from TLR. MI, myocardial infarction; TLR, target lesion revascularization; TVR, target vessel revascularization.

 

After discharge, 93.3% of the patients were successfully contacted. The median follow-up was 361 days, including censored patients, with a maximum of 768 days. At 30 days of follow-up, there were no deaths or TLR, there was 1 myocardial infarction (0.6%), TVR occurred in 0.6%, and 6 patients were readmitted to hospital due to a coronary syndrome (4.1%). At the 1-year follow-up, mortality was 0%, myocardial infarction occurred in 3.4%, TLR in 2.5%, TVR in 6.3%, and coronary-related rehospitalizations in 11.8%. At 18 months, the TLR rate was 4.3%. When all available follow-up was included (figure 2), mortality was 0%, myocardial infarction occurred in 5.4% (95% confidence interval [95%CI], 0.69-10.1), TLR in 8.4% (95%CI, 0-17.8), and TVR in 14.2% (95%CI, 3.61-24.78). During follow-up, none of the patients underwent surgical revascularization.

Figure 2. Survival curves of key clinical outcomes. Kaplan-Meier estimates for survival free from myocardial infarction (A), target lesion revascularization (B), and target vessel revascularization (C) in days. 95%CI, 95% confidence interval; TLR, target lesion revascularization; TVR, target vessel revascularization.

 

DISCUSSION

This is the first study to describe a real-world experience with the Essential Pro DEB for the treatment of ISR. In this cohort, all attempts at DEB delivery were successful, and less than 1 in 20 patients required bail-out stenting. The use of this new-generation DEB catheter was associated with high efficacy and a low incidence of adverse clinical outcomes during follow-up.

Patients with ISR are at higher risk of recurrent events than those undergoing non-ISR angioplasty.10 The annual rate of ISR requiring TLR is around 2%,3 representing up to 11% of all percutaneous coronary interventions performed in the United States.11,12 Notably, 52% of patients presenting with symptomatic ISR have unstable angina, and up to 27% have an acute myocardial infarction.12 Therefore, ISR poses a significant clinical challenge due to both its frequency and severity. The use of DEB in the ISR scenario avoids the addition of extra stent layers, which may have detrimental effects in the long term.

The use of DEB in ISR poses certain challenges. DEB platforms commonly have lower lesion crossability than regular coronary balloon catheters. DEBs also have larger profiles than conventional balloons making it difficult to cross the lesion and requiring aggressive maneuvers that could lead to a loss of coating drug during delivery.13 However, in our study, all attempted DEB deployments were successful. This high success rate may be due to improvements in second-generation DEBs, as well as better lesion evaluation and lesion preparation.

In the present study, TLR occurred in 2.5% of the patients and TVR in 6.3% at 1 year, while TLR occurred in 4.3% at 18 months. This event rate may seem low when compared with a prior systematic review of randomized and observational studies, which reported a TVR rate after DEB treatment of 11.3% with a calculated weighted mean follow-up of 18 months.14 In a recent investigational device exemption randomized trial for a paclitaxel-coated balloon in ISR, the rate of TLR at 1 year was 13%.15 However, prior evidence stems from diverse settings, designs, and populations, making it difficult to draw strong conclusions.

The rate of TLR with the previous generation of the Essential Pro DEB in a smaller cohort (n = 31) was 10% at 6 months.16 While this rate may seem higher than that reported in our study, the small number of events (n = 3) makes comparisons challenging.

Limitations

This study has some limitations. First, it was based on a real-world cohort involving different operators from the same center, which does not follow specific protocols. Only a quarter of the patients underwent angioplasty assessment guided by intracoronary imaging. The lack of sponsorship to cover intracoronary imaging costs and its limited use reflects the usual clinical practice of this center. During the performance of this study, few patients with ISR were treated with other DEB catheters due to the lack of specific DEB sizes in stock. Since this situation was rare and was unrelated to clinical or medical coverage characteristics, it is unlikely to introduce significant bias. Since this was a substudy of a larger DEB cohort, some variables specific to ISR, such as the time from prior stent implantation or the type of stent used, were not available.

Second, there were no dedicated follow-up visits for this study. Although most of these patients were followed up by local cardiologists who maintained regular medical records, some required telephone contact for follow-up. Third, angiographic assessment was not duplicated, and no core lab was available. Finally, the number of events was low despite consecutive enrollment from late 2020, impacting the precision of Kaplan-Meier estimates for key clinical outcomes. Some limitations are related to real-world practice settings, which, on the other hand, enhance external validity with less selection bias compared with other more controlled designs.

CONCLUSIONS

Among patients with ISR, the Essential Pro DEB catheter had a high delivery rate and a low incidence of adverse clinical outcomes during follow-up. These results further underscore the safety and efficacy of this new-generation DEB for patients with ISR.

FUNDING

This work received no industry sponsoring or funding.

ETHICAL CONSIDERATIONS

This study was approved by our local institutional review board at the Instituto Cardiovascular de Buenos Aires, and patients provided written informed consent to use their anonymized information for research purposes before their inclusion. Possible sex/gender biases have been considered in the preparation of this paper.

STATEMENT ON THE USE OF ARTIFICIAL INTELLIGENCE

No artificial intelligence tool was used in the preparation of this study.

AUTHORS’ CONTRIBUTIONS

L. Padilla conceived and oversaw all the process. F. Liberman, J. Tello, P. Rosas, P. Spaletra, G. Pedernera, P. Mascolo, S. Ordoñez, P. Santilli, and A. Candiello collected data and analyzed coronary angiograms. F. Cura and J. Belardi provided senior advice. P. Lamelas performed the statistical analysis and generated the first draft of the manuscript.

CONFLICTS OF INTEREST

L. Padilla has received proctoring and consulting honoraria from Terumo and Boston Scientific. P. Spaletra has received honoraria from Boston Scientific. F. Cura has received honoraria from Medtronic, Boston Scientific, Terumo, and Meril. P. Lamelas has received proctoring and consulting honoraria from Medtronic, Boston Scientific, Meril, Microport. The remaining authors have no conflicts of interest to declare.

 

REFERENCES

INTRODUCTION

The left main coronary artery (LM) supplies 84% of the blood flow to the left ventricle in patients with right dominance,1 making LM disease the coronary lesion with the worst prognosis. The prevalence of this disease is not negligible, as it is found in 4.8% of coronary angiograms,2 highlighting the prognostic importance of these lesions. Conservative treatment is a rarely a feasible option due to the high rate of cardiac adverse events during short-term follow-up, with a mortality rate exceeding 50%.3

Coronary artery bypass grafting (CABG) has traditionally been the most widely accepted revascularization strategy.4 In recent years, there have been significant pharmacological and technological improvements in percutaneous revascularization techniques, such as drug-eluting stents and intracoronary diagnostic techniques.5 These improvements, together with comparative studies, have prompted discussion on the various alternatives.6 Presently, the choice of revascularization strategy should be based on the complexity of the coronary anatomy and surgical risk.7

However, evidence is limited in older adults who are scarcely represented in classic studies. Furthermore, in these patients, frailty is a frequent and unstudied characteristic that can influence their prognosis. In this special population, CABG is usually ruled out due to high-surgical risk. On the other hand, percutaneous coronary intervention (PCI) could be a potential therapeutic option, although with little evidence to date.8 Consequently, we postulated that PCI of the LM might be feasible and safe in older patients, with a low incidence of associated complications and an acceptable rate of major adverse cardiac events (MACE) during follow-up.

METHODS

Study design

We conducted a retrospective, single-center study of older patients diagnosed with LM disease who underwent PCI. The study aimed to evaluate mid-term clinical outcomes and examine the prognostic significance of frailty in these patients. The study protocol was approved by the local clinical research ethics committee according to institutional and good clinical practice guidelines. Recruitment took place from January 2017 to December 2021 at Hospital Universitario Reina Sofía (Cordoba, Spain). Patients were eligible if they were aged ≥ 75 years at the time of LM disease diagnosis, and PCI was chosen as the treatment after deliberation by heart team discussion, or due to instability requiring emergent revascularization. Exclusion criteria consisted of end-stage chronic diseases, patients under palliative care, contraindications to dual antiplatelet therapy, and incomplete follow-up data. Included patients were grouped according to frailty status, determined by the FRAIL scale, with patients scoring 3 or more points considered frail.9 Definitions are shown in the supplementary data.

Outcomes

The main objective of the study was to describe mid-term clinical outcomes in older patients undergoing LM-PCI. We also aimed to compare clinical events according to the presence of frailty. The primary endpoint was a composite of MACE, defined as a composite of cardiovascular death (including death of uncertain cause), nonfatal myocardial infarction, the need for new revascularization, and stroke. Secondary outcomes were the individual components of MACE and all-cause mortality.

Angiographic analysis

Quantitative analysis of the coronary arteries was performed using the validated CAAS system (Pie Medica Imaging, the Netherlands). The basal anatomy of the LM bifurcation with the anterior descending artery and the circumflex artery was classified according to the Medina classification.10 The measurements analyzed included the reference diameter of the LM and its percentage of stenosis. The complexity of the coronary anatomy was studied using the SYNTAX scale.6

Statistical analysis

Categorical data are presented as counts (percentages), while continuous data are expressed as mean ± standard deviation or median [interquartile range]. Between-group comparisons were performed using the chi-square test or the Fisher exact test for categorical variables and the Student t-test or the Mann-Whitney U test for continuous variables. Kaplan-Meier curves and Cox regression models were used to analyze clinical events according to frailty. Inverse probability of treatment weighting (IPTW) was used to account for clinical differences between the 2 groups.11 Propensity scores were calculated using a logistic regression model that included the following covariates: age, sex, left ventricular ejection fraction, atrial fibrillation, chronic kidney disease, anemia, and chronic obstructive pulmonary disease. Standardized mean differences before and after weighting were used to evaluate the balance of the groups regarding the covariates. A difference of < 10% was considered to indicate a satisfactory balance. The distributions of the propensity scores before and after weighting were plotted to assess the degree of overlap between the 2 groups. Confidence intervals for the IPTW coefficients were obtained using robust sandwich-type variance estimators (figure 1 of the supplementary data).12 All tests were 2-tailed and significance was set at P < .05. Statistical analyses were performed using SPSS software (V 24; IBM Corp., United States) and R software (V4.0.3; R Foundation for Statistical Computing, Austria).

Figure 1. Main events to follow-up. CV, cardiovascular; MACE, mayor adverse cardiovascular events; MI, myocardial infarction; NS, nonsignificant; PCI, percutaneous coronary intervention. * P < .005.

RESULTS

During the study period, our hospital treated 437 patients with significant LM lesions percutaneously. Of them, a total of 140 patients met the inclusion criteria and were included in the analysis (figure 2 of the supplementary data).

Figure 2. Kaplan-Meier Curves of the primary outcome and mortality. CV, cardiovascular; MACE, major adverse cardiovascular events.

Baseline characteristics

The baseline clinical characteristics, clinical presentation and antithrombotic treatment administered are detailed in table 1. The median age of the patients was 80 [78-84] years and 36% (51 patients) were women. Most of the patients had a history of hypertension (84%, 118 patients) and 58% (81 patients) were diabetic. More than a third of the patient cohort had a previous personal history of ischemic heart disease (37%, 52 patients) and 33% (46 patients) had chronic kidney disease. Among noncardiovascular comorbidities, active cancer was present in 11 patients (8%) and prior blood transfusions had been required in 16 patients (11%). The mean EuroSCORE II was 3.07 [1.96-5.7] to assess surgical risk. Forty-eight patients (34%) had left ventricular systolic dysfunction at the time of revascularization.

Table 1. Patients’ baseline characteristics

Characteristics	Total n = 140	Nonfrail n = 72 (51)	Frail n = 68 (49)	P
Baseline clinical characteristics
Age, years	80 [78-84]	80 [77-84]	80 [78-84]	.090
Female sex	51 (36)	18 (25)	33 (49)	.004
Hypertension	118 (84)	61 (85)	57 (84)	.884
Diabetes	81 (58)	36 (50)	45 (66)	.053
Hypercholesterolemia	112 (80)	56 (78)	56 (82)	.999
Smoking history	7 (5)	5 (7)	2 (3)	.442
Previous ischemic heart disease	52 (37)	31 (43)	21 (31)	.136
Chronic kidney disease	46 (33)	22 (33)	24 (39)	.481
Atrial fibrillation	22 (16)	7 (10)	15 (22)	.041
Peripheral artery disease	20 (14)	14 (20)	6 (9)	.073
COPD	17 (12)	6 (8)	11 (16)	.156
Previous stroke	16 (11)	10 (14)	6 (9)	.073
Valve disease	15 (11)	7 (7)	10 (15)	.114
Anemia	29 (21)	10 (14)	19 (28)	.040
Active cancer	11 (8)	7 (10)	4 (6)	.399
Liver disease	4 (3)	3 (4)	1 (2)	.339
Previous blood transfusions	16 (11)	5 (7)	11 (16)	.086
Recent surgery or trauma	38 (27)	19 (26)	19 (28)	.836
EuroScore II	3.07 [1.96-5.7]	2.76 [1.83-4.18]	3.80 [2.04-7.85]	.010
Glomerular filtration rate (mL/min)	71.4 [48.4-87.3]	76.71 [51.01-87.51]	61.40 [41.40-81.85]	.072
Creatinine (mg/dL)	1.02 [0.87-1.30]	1.00 [0.80-1.85]	1.03 [0.90-1.50]	.109
Hemoglobin (mg/dL) (mean, ±SD)	12.6 (± 2)	13.02 (± 2)	12.16 (± 1.9)	.017
Hematocrit	38.6 [34.6-43.0]	39.6 [36.0-44.7]	36.6 [33.9-42.1]	.031
Platelets (× 109/L)	208 [171-246]	211 [182-244]	196 [160-250]	.340
Hs-cTnI (ng/L)	954 [40-7352]	2250 [30-10 000]	650 [40-5600]	.245
LVEF	60 [39-67]	60 [45-68]	58 [35-63]	.245
LV systolic dysfunction	48 (34)	20 (32)	28 (46)	.106
Clinical presentation
Acute coronary syndrome	85 (61)	45 (63)	40 (59)	.656
NSTEMI	61 (44)	28 (39)	33 (49)	.250
STEMI	9 (6)	6 (8)	3 (4)	.495
Unstable angina	15 (11)	11 (15)	4 (6)	.101
Chronic coronary syndrome	55 (39)	27 (38)	28 (41)	.656
Antiplatelet therapy
Dual antiplatelet therapy	104 (74)	57 (79)	47 (69)	.174
Aspirin + clopidogrel	61 (43)	31 (43)	30 (44)	.899
Aspirin + ticagrelor	43 (31)	26 (36)	17 (25)	.154
Triple antiplatelet therapy
Aspirin + clopidogrel + anticoagulant	36 (26)	15 (2)	21 (31)	.174
COPD, chronic obstructive pulmonary disease; Hs-cTnI, high sensitivity cardiac troponin I; LV, left ventricle; LVEF, left ventricular ejection fraction; NSTEMI, non-ST-elevation myocardial infarction; STEMI, ST-segment elevation myocardial infarction. Data are expressed as No. (%), mean ± standard deviation or median [interquartile range].

The most common clinical presentation was acute coronary syndrome (85 patients, 61% of cases). Among these, onset consisted of ST-segment elevation myocardial infarction (STEMI) in 9 patients (6%), non-ST-segment elevation myocardial infarction in 61 patients (44%), and unstable angina in 15 patients (10%). The remaining patients (55, 39%) presented with chronic coronary syndrome.

A total of 104 patients (74%) were discharged with dual antiplatelet therapy. The main combination was aspirin and clopidogrel (61 patients, 43%). In 36 patients (26%), initial triple therapy (anticoagulation and dual antiplatelet therapy) was chosen due to concurrent conditions requiring chronic oral anticoagulation.

Based on the FRAIL scale, almost half of the patients (68 patients, 49%) met clinical criteria for frailty at the time of revascularization. The baseline characteristics of frail and nonfrail patients are shown in table 1. No statistically significant differences were found in terms of age, main cardiovascular risk factors or noncardiovascular comorbidities between the 2 groups. However, compared with nonfrail patients, those with frailty were more likely to be female (49% vs 25%; P = .004), to have atrial fibrillation (22% vs 10%; P = .041), a higher EuroSCORE level (3.80 vs 2.76; P = .010), and anemia (28% vs 14%; P = .040), and consequently a lower hematocrit and hemoglobin value (36.6% vs 39.6%; P = .031 and 12.16 mg/dL vs 13.02 mg/dL; P = .017, respectively).

Angiographic and procedural characteristics

Angiographic and procedural data are shown in table 2. The arterial access of choice was radial access (81% of procedures, 113 patients). A median SYNTAX score of 21 [15-29.5] was observed in 96 patients (68%) with multivessel disease, and 62 patients (44%) had a SYNTAX score > 22. The most common angiographic involvement of the LM was the distal segment (61%, 86 patients), while the most common plaque distribution according to the Medina classification was “1,1,1” (35 patients, 41% of LM bifurcation lesions). The strategy of choice for the treatment of the bifurcation was the provisional stent strategy (85% of LM bifurcation lesions, 73 patients), while the upfront 2-stent strategy was used in only 13 patients (15% of the LM bifurcation lesions). The mean diameter of the LM was 4.1 [± 3.5-4.5] mm with a mean angiographic stenosis of 62% (± 7). In 59 patients (42%), the procedure was guided using intravascular imaging techniques (58 patients using intracoronary ultrasound and 1 patient using coherence tomography). Coronary physiology was used in 5 patients (4%) to guide the need for revascularization or to check the result after percutaneous treatment. In 7 (5%) patients, mechanical support was required, either due to cardiogenic shock, or as a preventive measure in high-risk angioplasty (5 patients with an intra-aortic balloon pump and 2 with an Impella CP device [Abiomed, United States]). Intraprocedural complications occurred in 8 patients (6%), including a major complication in 4 patients (3 intraprocedural deaths and 1 cardiogenic shock), and a minor complication in 4 patients (1 coronary dissection with Thrombolysis in Myocardial Infarction (TIMI) grade 3 distal flow, 1 pseudoaneurysm, and 2 bleeding events from the femoral access resolved by stent implantation). The LM diameter was larger in patients with frailty than in those without (4 mm [4-4.5] vs 3.5 mm [3.5-4.5]; P = .023), a paradoxical finding since the percentage of women was higher in the group with frailty percentage of women. However, this information did not seem to be clinically relevant. No other clinically relevant differences were found between the 2 groups (table 2).

Table 2. Patients’ angiographic and procedural characteristics

Characteristics	Total n = 140	Nonfrail n = 72 (51)	Frail n = 68 (49)	P
Angiographic characteristics
Multivessel disease	96 (68)	50 (69)	46 (68)	.819
SYNTAX score	21 [15-29,5]	21 [17-28.5]	21.5 [14-30.6]	.752
SYNTAX score > 22	62 (44)	25 (39)	31 (46)	.463
LM diameter (mm)	4 [3.5-4.5]	3.5 [3.5-4.5]	4 [4-4.5]	.023
LM stenosis	62 (± 7)	64 (± 6)	61 (± 5)	.342
LM bifurcation	86 (61)	39 (54)	47 (69)	.069
Medina (1,1,1)	35 (41)	20 (51)	15 (32)	.690
Medina (1,1,0)	33 (39)	10 (26)	23 (49)	.027
Medina (1,0,1)	8 (9)	3 (8)	5 (11)	.724
Medina (0,1,1)	3 (3)	2 (5)	1 (2)	.588
Medina (1,0,0)	4 (5)	1 (3)	3 (6)	.623
Medina (0,1,0)	0 (0)	0 (0)	0 (0)	-
Medina (0,0,1)	3 (3)	3 (8)	0 (0)	.089
Intracoronary diagnostic technique
Intravascular imaging	59 (42)	28 (39)	31 (46)	.422
IVUS	58 (41)	28 (39)	30 (44)	.530
OCT	0 (0)	0 (0)	1 (2)	.486
Intracoronary physiology test	5 (4)	4 (6)	1 (2)	.367
Procedure characteristics
Radial access	113 (81)	60 (83)	53 (78)	.253
Contrast (mL)	200 [160-255]	215 [150-259]	200 [160-250]	.553
Temporary pacemakers	6 (4)	3 (4)	3 (4)	1.000
LV assist devices	7 (5)	4 (6)	3 (4)	1.000
Intra-aortic balloon pump	5 (4)	4 (6)	1 (2)	.367
Impella	2 (1)	0 (0)	2 (3)	.239
One-stent bifurcation technique	73 (85)	34 (87)	39 (83)	.588
Stent MB + kissing	20 (27)	12 (35)	7 (18)	.077
Two-stent bifurcation technique	13 (15)	5 (13)	8 (17)	.636
T stenting	3 (23)	2 (40)	1 (12.5)	.498
TAP	2 (15)	0 (0)	2 (25)	.498
Culotte	5 (39)	1 (20)	4 (50)	.371
DK-Crush	2 (15)	1 (20)	1 (12.5)	1.000
SKS	1 (8)	1 (20)	0 (0)	.413
MB stent diameter (mm)	3.5 [3-3.5]	3.5 [3-3.5]	3.5 [3-3.5]	.877
MB stent length (mm)	18 [15-18]	18 [15-18]	18 [15-18]	.896
SB stent diameter (mm)	3.5 [3-3.5]	3.25 [2.8-3.5]	3.5 [3-3.6]	.371
SB stent length (mm)	15 [12-18]	15.5 [15-21]	15 [11-18]	.342
Complications
Intraprocedural complications	8 (6)	6 (8)	2 (3)	.157
Major	4 (3)	3 (4)	1 (2)	.356
Minor	4 (3)	3 (4)	1 (2)	.356
DK, double kissing; IVUS, intravascular ultrasound; LM, left main; LV, left ventricle; MB, main branch; OCT, optical coherence tomography; SB, side branch; SKS, simultaneous kissing stents. TAP, T and small protrusion. Data are expressed as No. (%), mean ± standard deviation or median [interquartile range].

Clinical results at follow-up

After a median follow-up of 19 months [5-35], a total of 40 (29%) MACE were recorded: 3 (2%) patients had a nonfatal myocardial infarction, 7 (5%) patients required repeat revascularization (3 for restenosis of the LM, and 4 in a different vessel), and 30 patients (21%) died of cardiac and/or uncertain causes. No strokes were reported during follow-up. Sixteen patients (11%) died of noncardiac causes during follow-up.

Clinical outcomes are presented in figure 1 and figure 2. No independent predictor of MACE was identified. The independent predictors of all-cause mortality were left ventricular ejection fraction (hazard ratio [HR], 0.90 [0.96-0.99]; P = .014), chronic kidney disease (HR, 2.26 [1.16-4.42]; P = .017), and particularly the presence of frailty (HR, 2.42 [1.17-5.02]; P = .018) (table 1 of the supplementary data). The primary endpoint of MACE occurred in 24 (35%) patients in the frail group and in 16 (22%) patients in the nonfrail group (HR, 1.61 [0.79-3.28]; P = .193). Frail patients had an increased risk of cardiovascular mortality: 21 (31%) vs 9 (13%); HR, 2.64 (1.21-5.77); P = .015. All-cause mortality was also more frequent in the frail group: 33 (49%) vs 13 (18%); HR, 2.94 (1.55-5.59); P = .001). The events during follow-up are presented in table 2 of the supplementary data. After IPTW adjustment, only the difference in all-cause mortality remained significant (HR, 1.95 [1.02-3.75]; P = .046). Survival analysis of the weighted population is shown in figure 3.

Figure 3. Kaplan-Meier Curves of the secondary outcomes. CV, cardiovascular; IPTW, inverse probability of treatment weighting; MACE, major adverse cardiovascular events.

DISCUSSION

The present study describes the feasibility of LM-PCI in a cohort of older patients. The main results were as follows: a) the rate of MACE at mid-term follow-up was 29%, mainly driven by cardiovascular and/or uncertain cause death; b) a high percentage of frailty was found in our population (49%); c) frail patients had a 2-fold increased risk of all-cause mortality during follow-up (HR, 1.95 [1.02-3.75]; P = .046) (figure 4).

Figure 4. Central illustration. Results of percutaneous treatment of LM in elderly patients and impact of frailty. CV, cardiovascular; LM, left main coronary artery; MACE, major adverse cardiovascular events; MI, myocardial infarction; NS, non-significant; PCI, percutaneous coronary intervention.

The treatment of LM disease has traditionally been surgical, given the complexity involved and significant prognostic impact.13 However, the marked advances in interventional cardiology in recent decades have modified the approach.14,15 Contrasting evidence from clinical trials and meta-analyses shows that percutaneous treatment has similar results to surgical approaches in terms of mortality, acute myocardial infarction, and stroke at 5 years of follow-up.16 This shift has is reflected in the evolving recommendations in clinical practice guidelines, and the current European revascularization guidelines assign a grade of recommendation IA to both surgical and percutaneous strategies for the treatment of LM disease when the anatomy is not complex (SYNTAX < 22), and a class IIa recommendation for cases of intermediate complexity (SYNTAX 23-32).7

Nevertheless, the population analyzed in the study has specific clinical characteristics, and is not usually represented in large clinical trials (older patients and those with frailty and a high burden of associated comorbidities). These variables are not systematically included in surgical risk scores but are generally taken into account in routine clinical practice and often influence heart team decisions on the treatment strategy.17 Therefore, because this particular patient cohort is often excluded from research, there are no conclusive data on the benefit of percutaneous revascularization.

Our results are in line with those of previous registries in terms of MACE and all-cause mortality, as well as the association between age and a marked incidence of mortality due to noncardiac causes during follow-up. However, unlike earlier studies, we observed no differences in cardiovascular mortality, despite these patients having a more complex coronary anatomy than younger patients.18 In this regard, our study cohort had a median SYNTAX score of 21, and 44% of the patients had a score above 22. Like previous studies, this SYNTAX index score was not associated with a higher probability of cardiac events during follow-up in this special population.

In the present study, rates of acute myocardial infarction and new revascularization of the target lesion were lower than in other cohorts. Although it is difficult to make direct comparisons, we postulate that the use of new-generation drug-eluting stents and a higher proportion of revascularization guided by intracoronary diagnostic techniques may have influenced this finding. However, the use of intracoronary imaging techniques in our study was relatively low (42%) considering their benefit in patients with complex coronary lesions.19

In recent years, there has been growing interest in understanding the impact of comorbidities and frailty in older patients with cardiovascular disease.20,21 Several studies have compared invasive strategies with conservative approaches in older patients, demonstrating benefits for revascularization.22,23 However, the MOSCA-FRAIL trial compared both strategies in frail patients and observed that an invasive strategy did not confer additional benefit compared with conservative management of these patients, despite a fairly low percentage of LM disease.24 In our study, we observed a 2-fold increase in the risk of all-cause mortality in patients with frailty, suggesting the need to add systematic evaluation of frailty in older patients undergoing LM-PCI. Such assessment can aid in selecting the optimal therapeutic strategy, taking into account the likelihood of mortality during follow-up, irrespective of the application of an invasive strategy in coronary disease. These results, moreover, are consistent with other cardiovascular diseases with significant prevalence and mortality, such as heart failure.25

Study limitations

The present study has several limitations. First, it has the limitations inherent to its observational and retrospective design. Although the sample size is relatively small, it represents the largest study specifically focused on LM-PCI in older patients and analyses associated comorbidities and their impact on cardiovascular adverse events. Second, the absence of a control group receiving conservative treatment hinders the ability to draw more robust conclusions on the safety and efficacy of LM-PCI in these patients. In addition, the selection of cutoff points (age ≥ 75 years) to define this cohort of older patients was arbitrarily based on the exclusion criteria of the main clinical trials previously published. A high percentage of patients with frailty may not have undergone revascularization and would therefore have been excluded from the study. Regarding the prognostic significance of frailty, although we used IPTW to reduce confounding bias, we cannot rule out the possibility of residual confounding due to unmeasured covariables. Furthermore, there are no data on bleeding events during follow-up, which is an important concern given the impact of antiplatelet therapy in these patients. Finally, the percentage of intracoronary imaging use was lower than expected.

CONCLUSIONS

In real-life patients with advanced age and multiple associated comorbidities, percutaneous treatment of LM could be considered a feasible option, with an acceptable incidence of adverse cardiovascular events during follow-up and a low incidence of complications associated with the procedure. Frailty was an independent predictor of all-cause mortality during follow-up. When weighing the risks of LM-PCI in older patients, frailty should be taken into account in the therapeutic decision-making process.

FUNDING

None.

ETHICAL CONSIDERATIONS

The study protocol was approved by the Local Clinical Research Ethics Committee according to institutional and Good Clinical Practice guidelines. All patients signed the informed consent for publication. The authors confirm that sex and gender variables have been considered in accordance with the SAGER guidelines.

STATEMENT ON THE USE OF ARTIFICIAL INTELLIGENCE

No artificial intelligence was used in the preparation of the study.

AUTHORS’ CONTRIBUTIONS

I. Gallo, M. Alvarado and J. Perea contributed to data collection. R. González-Manzanares performed the statistical analysis. J. Suárez de Lezo and M. Romero contributed to the interpretation of the results. I. Gallo and F. Hidalgo wrote the manuscript. S. Ojeda and M. Pan reviewed the manuscript.

CONFLICTS OF INTEREST

S. Ojeda is associate editor of REC: Interventional Cardiology. The journal’s editorial procedure to ensure impartial processing of the manuscript has been followed. S. Ojeda has received consulting fees from Medtronic and Edwards and speaker fees from Philips, World Medical and Boston Scientific and is holder of a research grant (PI21/00949) from the Spanish Ministry of Science and Innovation (Instituto de Salud Carlos III). M. Pan has received speaker fees from Abbott, Boston Scientific, World Medical and Philips and holds a research grant (PI21/00949) from the Spanish Ministry of Science and Innovation (Instituto de Salud Carlos III). The remaining authors declare no conflicts of interest.

REFERENCES

INTRODUCTION

Fractional flow reserve (FFR) measurement is an invasive procedure performed during coronary angiography to determine the functional significance of coronary stenoses.

In recent years, the instantaneous wave-free ratio (iFR) resting index has been developed to assess the functional significance of coronary stenoses without the need for adenosine administration. The optimal iFR cutoff value—equivalent to 0.80 in FFR—was initially established at 0.89.1 In 2017, 2 clinical studies comparing FFR with iFR found no significant differences in clinical outcomes at follow-up.2-3 After the publication of these 2 studies, the European Society of Cardiology guidelines on myocardial revascularization4 assigned resting indices the same grade of recommendation as FFR for the functional assessment of coronary lesions.

Despite the validation of these 2 techniques in clinical trials and their inclusion in clinical practice guidelines, up to 20% discordance has been reported between iFR+/FFR− or iFR−/FFR+5 Several clinical factors, such as diabetes,6 and anatomical factors, such as lesion location in the left main or proximal left anterior descending coronary arteries, have been identified in association with this discordance.7

Previous studies comparing FFR with iFR using a piezoelectric pressure sensor wire (PPSW) calculated the mean distal-to-aortic pressure ratio beginning 25% into diastole and ending 5 ms before end diastole.1

Recently, a new resting index—the diastolic pressure ratio (dPR)—has been developed to calculate the mean distal-to-aortic pressure ratio over the entire diastolic phase (from the lowest point of the dicrotic notch up to 50 ms before the onset of the upstroke of the next beat)8 using a fiber-optic sensor wire (FOSW).

A study that compared the values of different resting indices (iFR, dPR, dPR25-75, dPRmid, iFRmatlab, iFR50ms, and iFR100ms) revealed that all were numerically identical,8 meaning that the results obtained with the iFR can be extrapolated to other resting indices.

To date, no study has compared the agreement between dPR and FFR measured using a FOSW. One advantage of the FOSW over the PPSW is the lower loss of mean pressure matching in the wire compared with the measurement obtained in the guide catheter (drift).9 Although various iFR studies state that drifts < ± 0.02 are considered acceptable, the drifts reported with the FOSW were even lower at < ± 0.01.10

The diagnostic reproducibility of PPSW decreases significantly when close to the threshold value of 0.80 and is approximately 80% when measurements are < 0.77 or > 0.83, and around 90% with values < 0.76 or > 0.84.11 Since the FOSW is less sensitive to changes in humidity and temperature, greater reproducibility of results can be expected when the measurement is repeated.

Considering that most discordant measurements have been associated with cutoff values, the better reproducibility of measurements and practically nonexistent drift of the FOSW can more accurately determine FFR and dPR measurements and reduce discrepancies.

METHODS

Study design

In this prospective, observational, and multicenter registry of consecutive coronary stenoses, we conducted a study with FOSW based on our routine clinical practice.

We included consecutive patients with clinical signs and coronary angiography findings suggesting the need for a functional study with a pressure wire. We excluded patients with cardiogenic shock, heart failure, severe anemia (hemoglobin < 10 mg/dL), heart rate < 50 or > 100 bpm, baseline systolic blood pressure < 90 mmHg or > 160 mmHg, severe coronary artery lesions in distal segments, and contraindications for the administration of adenosine.

Objective

The aim of this study was to evaluate the incidence and factors related to diagnostic discrepancies between these indices using the FOSW. Secondary aims consisted of assessing the diagnostic reproducibility of FOSW in 2 consecutive measurements of FFR and dPR and evaluating the drift rate.

Procedure

The study was approved by the Drugs Research Ethics Committee of the Basque Country (internal code PS 2019039). All patients received information on the study and were asked to sign a written informed consent form prior to their participation in the study.

We performed coronary angiography using standard methods, with visual estimation of severity after intracoronary nitroglycerin administration. We included lesions with up to 50% to 75% percent diameter stenosis and collected data on the reference luminal diameter, minimum luminal diameter, lesion length, calcification, and vessel tortuosity for each studied lesion.

We performed 2 consecutive measurements of dPR (threshold, 0.89) and FFR (threshold, 0.80) for each studied lesion and analyzed the clinical and angiographic factors to determine their correlation with discordance (FFR−/dPR+ and FFR+/dPR−). We took dPR1 and FFR1 as reference values for discrepancy analysis.

We conducted the FOSW functional study with 5-, 6-, or 7-Fr guide catheters without side holes, using an OptoWire (Opsens Medical, Canada). After advancing the wire toward the tip of the guide catheter, we removed the introducer sheath and flushed the system with saline solution to prevent damping of the pressure wire resulting in equal pressure of the wire and the guide catheter at the tip of the catheter. After advancing the pressure wire distally, we administered 200 μg of intracoronary nitroglycerin before taking any measurements. We took the 2 dPR measurements after waiting the necessary time to obtain confirmation of a stable baseline distal-to-aortic coronary pressure ratio (Pd/Pa).

Subsequently, we took 2 different FFR measurements. Hyperemia was induced according to standard practice in each center (through intracoronary or IV adenosine infusion). If intracoronary adenosine was infused, for the second measurement, we waited until the baseline heart rate, blood pressure, and Pd/Pa were regained and then infused the same dose of adenosine. If IV adenosine was infused, the infusion was stopped until baseline heart rate, blood pressure, and Pd/Pa were regained, and then we infused adenosine at the same rate.

We evaluated the presence of drift upon removal of the pressure wire from the guide catheter. Drift was defined as a difference in Pd/Pa of at least ± 0.02 upon removal of the pressure wire from the guide catheter. In the presence of significant drift, measurements were repeated.

Cutoff values

The cutoff value was ≤ 0.80 for FFR and ≤ 0.89 for dPR.10 We categorized all studied vessels based on dPR and FFR values into 4 groups: concordant positive group (FFR ≤ 0.80 and dPR ≤ 0.89), concordant negative group (FFR > 0.80 and dPR > 0.89), discordant FFR+/dPR− group (FFR ≤ 0.80 and dPR > 0.89), and discordant FFR−/dPR+ group (FFR > 0.80 and dPR ≤ 0.89).

Statistical analysis

Continuous variables are expressed as mean and standard deviation, while categorical variables are expressed as percentages. We measured the association between continuous variables using Pearson’s correlation coefficient. To determine differences in variables in the FFR/dPR concordance groups we used ANOVA (for continuous variables) and the chi-square test (for categorical variables). We used the chi-square test to assess how each variable impacted FFR−/dPR+ and FFR+/dPR− discrepancies, and a multiple logistic regression model with backward elimination to determine the factors impacting FFR−/dPR+ and FFR+/dPR− discrepancies. On univariate analysis, we included variables with P < .1 in the logistic regression analysis and excluded those with a total n < 10. The analysis was conducted using SPSS software (version 20.1) and R (version 4.0.4).

RESULTS

We included a total of 428 stenoses in 361 patients. Table 1 and table 2 show the patients’ baseline characteristics, clinical presentation, and procedural characteristics.

 

Table 1. Patients’ baseline characteristics

	N = 361
Age (years)	65.80 ± 10.5
Male sex	76.9
Hypertension	63.3
Diabetes mellitus	31
Hypercholesterolemia	60.4
Active/former smoker	19.7/40.5
Previous acute coronary syndrome	30.5
Atrial fibrillation	14.7
Heart failure/dysfunction	15.4
Peripheral artery disease	10
Valvular heart disease, previous bypass, stroke	< 6
Data are expressed as No. (%) mean ± standard deviation.

 

Table 2. Clinical presentation and procedural characteristics

	N = 361
Clinical presentation	N = 361
Chest pain	45.8
Acute coronary syndrome	23.1
Unstable angina	7.1
Left ventricular dysfunction	9.9
Others	14.2
Procedural characteristics
Baseline systolic blood pressure (mmHg)	132 ± 24
Systolic blood pressure during hyperemia (mmHg)	125 ± 25
Baseline heart rate (bpm)	70 ± 12
Heart rate during hyperemia (bpm)	69 ± 15
Reference luminal diameter (mm)	3.09 ± 0.53
Stenosis (%)	54 ± 8
Lesion length (mm)	17.9 ± 12.2
IV/intracoronary adenosine	33/67
Catheter size (5-Fr/6-Fr)	17.5/81
Drift ≥ ± 0.02	5.7
dPR	0.90 ± 0.08
FFR	0.83 ± 0.08
dPR, diastolic pressure ratio; FFR, fractional flow reserve. Data are expressed as No. (%) mean ± standard deviation.

 

Sixty-seven percent of the patients received intracoronary adenosine; the mean doses of intracoronary adenosine administered were 324 μg (standard deviation [SD] ± 152) via the right coronary artery and 442 μg (SD ± 234) via the left coronary artery.

The medians of dPR measurements were 0.90 and 0.90 (SD ± 0.08) for the first and second measurements, with positivity rates of 27.4% and 27.9%, respectively. For FFR, the medians were 0.83 and 0.83 (SD ± 0.08) for the first and second measurements, with positivity rates of 28.1% and 30%, respectively.

The most widely studied vessel was the left anterior descending coronary artery (63%), followed by the left circumflex (20%) and right coronary arteries (16%).

The left anterior descending coronary artery showed a higher positivity rate (dPR+, 35.3%; FFR, 34%) than the left circumflex (dPR, 11.9%; FFR, 20.5%) and right coronary arteries (dPR, 15.9%; FFR, 17.4%).

Diagnostic reproducibility was 95.8% for dPR, with a correlation coefficient between the 2 measurements (dPR1 and dPR2) of 0.974 (P < .0001) and a mean difference of 0.019 (max, 0.12; min, −0.17). For dPR values < 0.86 or > 0.92, diagnostic reproducibility was 99.6%, decreasing to 90.7% when values were ≥ 0.86 or ≤ 0.92. For FFR, diagnostic reproducibility was 94.9%, with a correlation coefficient (FFR1 and FFR2) of 0.942 (P < .0001) and a mean difference of 0.029 (max, 0.14; min, −0.18) (figure 1). Values < 0.77 or > 0.83 showed a diagnostic reproducibility of 98.6%, decreasing to 86.4% when these values were ≥ 0.77 or ≤ 0.83.

Figure 1. Correlation coefficient and histogram of the differences between the 2 dPR and FFR measurements. dPR, diastolic pressure ratio; FFR, fractional flow reserve; SD, standard deviation.

 

The diagnostic concordance (figure 2) between FFR and dPR was 82%, with a correlation coefficient of 0.721 (P < .0001), while diagnostic discordance was 18.2% (FFR+/dPR–, 8.2% and FFR–/dPR+, 10.0%). In the FFR+/dPR– discordant group, FFR was 0.76 ± 0.04 and dPR, 0.93 ± 0.03. In the FFR–/dPR+ discordant group, FFR was 0.84 ± 0.03 and dPR, 0.86 ± 0.03.

Figure 2. Distribution of lesions according to FFR and dPR, with the rate of concordant and discordant measurements. dPR, diastolic pressure ratio; FFR, fractional flow reserve.

 

Out of the 75 discordant results reported, the measurements at the cutoff value (7 stenoses with FFR 0.80 and 18 stenoses with dPR 0.89) showed a discordance rate of 72%, which decreased as it moved away from the cutoff value (figure 3).

Figure 3. Probability of diagnostic discordance between FFR and dPR. The probability of discordance is close to 50% around the FFR cutoff point of 0.80 and decreases as it moves away from this point. Empirical model (bar chart) and model proposed by Petraco et al.11 (in grey). dPR, diastolic pressure ratio; FFR, fractional flow reserve.

 

Table 1 of the supplementary data illustrates the association between clinical and anatomical characteristics and the extent of agreement between FFR and dPR.

Out of all the variables analyzed in the multivariate analysis, hypertension (odds ratio [OR], 3.48, 95% confidence interval [95%CI], 1.01-11.98; P = .043) and intracoronary adenosine (OR, 7.04; 95%CI, 1.63-30.3; P = .001) were significantly associated with FFR–/dPR+ discordance. Age younger than 75 years (OR, 4.52; 95%CI, 1.03-20; P = .016) and percent diameter stenosis > 60% (OR, 6.69; 95%CI, 2.79-16; P < .001) were significantly associated with FFR+/dPR– discordance (table 3).

 

Table 3. Univariate analysis and multivariate logistic regression of variables associated with discordance

Variables	FFR+/dPR−				FFR−/dPR+
	Univariate analysis		Multivariate logistic regression		Univariate analysis		Multivariate logistic regression
	OR (95%CI)	P	OR (95%CI)	P	OR (95%CI)	P	OR (95%CI)	P
Age < 75 years	9.5 vs 3.3	.039	4.52 (1.03-20)	.016	7.1 vs 8.9	.347
Female sex	5.7 vs 8.9	.231			11.4 vs 6.2	.079
Hypertension	7.2 vs 10.4	.178			10 vs 2.2	.002	3.48 (1.01-11.98)	.043
Diabetes mellitus	7.3 vs 8.6	.406			11.7 vs 5.3	.018	2.11 (0.95-4.69)	.064
Dyslipidemia	7.5 vs 9.5	.304			7.1 vs 6.7	.525
HF/LV dysfunction	4.4 vs 9.0	.154			11.8 vs 6.7	.118
Valvular heart disease	7.7 vs 8.3	.635			19.2 vs 6.8	.037
Coronary calcification	6.7 vs 8.6	.387			5.3 vs 8	.302
Moderate/severe tortuosity	7.8 vs 8.3	.516			10.6 vs 5.7	.054
Left main coronary artery	0 vs 7.9	.612			50 vs 6.9	.007
Left anterior descending coronary artery	7.9 vs 7.6	.531			9.4 vs 4.4	.041
Right coronary artery	10.8 vs 7.1	.176			2.4 vs 8.8	.029
Left circumflex artery	4.3 vs 8.5	.179			2.9 vs 8.4	.081
RLD > 3 mm	6.6 vs 13.3	.049			7.5 vs 8	.518
Length > 20 mm	12.5 vs 5.4	.010			7.8 vs 7.3	.492
Stenosis > 60%	16 vs 3	< .001	6.69 (2.79-16)	< .001	5.8 vs 8.3	.227
Heart rate > 80 bpm	8.4 vs 8	.527			10.8 vs 6.8	.155
Intracoronary adenosine	7.4 vs 8.5	.713			13 vs 3.8	.004	7.04 (1.63-30.3)	.001
95%CI, 95% confidence interval; dPR, diastolic pressure ratio; FFR, fractional flow reserve; HF, heart failure; LV, left ventricle; OR, odds ratio; RLD, reference luminal diameter. Data are expresed in %.

 

The drift rate was 5.7%.

DISCUSSION

We present the results of the first study conducted with a FOSW capable of measuring the diagnostic variability of 2 consecutive determinations of nonhyperemic and hyperemic indices, as well as the diagnostic discordance between the 2 techniques.

Previous discordance studies between the 2 indices with PPSW revealed discordance rates ranging from 12% to 22%,12,13 largely depending on the proximity of the values to the cutoff point. In a study by Lee et al.,12 the mean iFR and FFR values were 0.95 ± 0.10 and 0.87 ± 0.11, respectively, with a discordance rate of 12%, while in a study by Warisawa et al.,13 the mean iFR and FFR values were 0.89 ± 0.05 and 0.80 ± 0.03, respectively, with a discordance rate of 22%. In our study, the discordance rate was 18.2%, with a mean dPR of 0.90 (SD ± 0.08) and a mean FFR of 0.83 (SD ± 0.08), which is a slightly lower discordance rate than that reported by previous studies on PPSW and mean iFR and FFR values close to the cutoff point, which may be indicative of the accuracy of measurements obtained with FOSW.

The main findings of this study were the excellent diagnostic reproducibility of the FOSW, the clinical and anatomical variables related to FFR/dPR discordance, and the low drift rate reported in the measurements.

Diagnostic reproducibility with the fiber-optic sensor wire

Diagnostic reproducibility with the FOSW was excellent, with a variation between 2 consecutive measurements < 0.02 for dPR and < 0.03 for FFR. This accuracy in measurement confers excellent diagnostic reproducibility. These data are better than those previously reported with PPSW.11

Clinical and anatomical variables associated with FFR/dPR discordance

For FFR+/dPR− discordance, in the multivariate analysis, only age younger than 75 years and percent diameter stenosis > 60% were significantly associated with FFR+/dPR− discordance. This discordance in participants younger than 75 years could be explained by a slower baseline flow and a greater coronary flow reserve in younger patients with preserved microvascular function.14,15 Although discordance due to a higher percent diameter stenosis has already been described in previous studies,15,16 such discordance requires a preserved coronary flow reserve.6 When arterial flow velocity significantly increases during hyperemia, the pressure gradient does so too, decreasing distal coronary pressure during hyperemia substantially compared with baseline values, resulting in a low FFR value.

For FFR−/dPR+ discordance, in the multivariate analysis, the associated variables were hypertension and the administration of intracoronary adenosine. Although hypertension has not been associated with FFR−/dPR+ discordance in previous studies, it is known that patients with hypertension and left ventricular hypertrophy have a reduced coronary flow reserve17 and a possible lack of vasodilatory response to adenosine due to an increased left ventricular end-diastolic pressure. These 2 factors could play a key role in the association between hypertension and FFR−/dPR+ discordance.

Although IV adenosine is the most widely studied route of administration to achieve maximum hyperemia, intracoronary adenosine at doses > 300 μg may be equally or more effective in achieving maximum hyperemia18 and with fewer adverse events.19 In our study, the FFR−/dPR+ discordance reported when intracoronary adenosine was used could be a result of a failure to achieve adequate hyperemia.

These variables related to discordance demonstrate that dPR and FFR measure different aspects of coronary circulation, which may be affected differently in distinct patients or myocardial territories, leading to discordant FFR values and nonhyperemic indices.20

Drift in the fiber-optic pressure wire

The incidence of drift in clinical studies of pressure wires is not well known, and the drift considered acceptable has varied over the years. Previously, FFR measurement was repeated when drift was > 5 mmHg,21 while in more recent studies, drift > 3 mmHg has been considered significant. When FFR is between 0.77 and 0.82, drift ≤ 3 mmHg can reclassify 18.7% of stenoses,22 and this reclassification may be higher when a nonhyperemic diastolic or whole-cycle index is used.23 In the CONTRAST trial analysis of the PPSW, the drift rate (Pd/Pa ± 0.03) was 17.5%,24 while a more recent study comparing drift between FOSW and PPSW revealed a significantly lower rate with the FOSW (4.8% vs 26.7%; P = .02).9 In our study, the drift rate was 5.7%, which is consistent with other studies on FOSW, and much lower than that reported with PPSW, facilitating the use of pressure wire in routine clinical practice.

Limitations

Our study has several limitations. Both the severity and length of coronary lesions were quantified by the operator’s visual estimation at the time of the procedure, and since this was a study without a core laboratory, we cannot rule out the possibility that some of the discrepancies found were due to technical problems in determining the indices. Since the study was based on our routine clinical practice, most patients received intracoronary adenosine, and the protocol did not specify the intracoronary infusion comprehensively, which may have resulted in the lower hyperemia reported in some patients.

Target lesion revascularization was based on dPR or FFR values according to the operators’ decision. Patient selection for pressure guidance evaluation was also left to the treating physician’s discretion, which may have resulted in biases. However, our intention was to study dPR and FFR indices under real-world conditions.

CONCLUSIONS

Although FFR and dPR measurements with FOSW have excellent reproducibility and a low incidence of drift, the discordance rate remains similar to that reported by previous studies with PPSW, and largely depends on the proximity of values to the cutoff point. Intracoronary adenosine and hypertension, which imply a lack of hyperemia or increased microvascular resistance, are associated with FFR−/dPR+ discordance. Age younger than 75 years and the severity of stenosis, which may be associated with a preserved coronary flow reserve, are related to FFR+/dPR− discordance.

FUNDING

This study received no funding.

ETHICAL CONSIDERATIONS

This study was approved by the Drugs Research Ethics Committee of the Basque Country (internal code PS 2019039) for its implementation. All patients received a patient information sheet about the study and signed an informed consent form before enrollment. The study took into consideration sex and gender variables before drafting this article.

STATEMENT ON THE USE OF ARTIFICIAL INTELLIGENCE

No artificial intelligence has been used.

AUTHORS’ CONTRIBUTIONS

M. Sádaba Sagredo drafted the protocol, included patients as the lead investigator of his center, and drafted the manuscript. A. Subinas Elorriaga and A. Quirós contributed to the statistical analysis and drafting of the manuscript. The remaining authors are lead investigators of the READI EPIC-14 trial in their respective centers and contributed to patient inclusion and article review.

CONFLICTS OF INTEREST

None declared.

SUPPLEMENTARY DATA

Supplementary data associated with this article can be found in the online version available at https://doi.org/10.24875/ RECIC.M24000448.

ACKNOWLEDGEMENTS

We wish to thank M.ª Ángeles Carmona for her support in data collection and patient inclusion.

REFERENCES