Diagnostic and Prognostic Efficacy of Coronary Flow Capacity Obtained Using Pressure-Temperature Sensor–Tipped Wire–Derived Physiological Indices
Author + information
- Rikuta Hamaya, MDa,
- Taishi Yonetsu, MDa,
- Yoshihisa Kanaji, MDa,
- Eisuke Usui, MDa,
- Masahiro Hoshino, MDa,
- Masao Yamaguchi, MDa,
- Masahiro Hada, MDa,
- Yoshinori Kanno, MDa,
- Tadashi Murai, MDa,
- Kenzo Hirao, MD, PhDb and
- Tsunekazu Kakuta, MD, PhDa,∗ (kaz{at}joy.email.ne.jp)
- aDivision of Cardiovascular Medicine, Tsuchiura Kyodo General Hospital, Ibaraki, Japan
- bDepartment of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan
- ↵∗Address for correspondence:
Dr. Tsunekazu Kakuta, Department of Cardiology, Tsuchiura Kyodo General Hospital, 4-4-1 Otsuno, Tsuchiura City, Ibaraki, 300-0028, Japan.
Graphical abstract
Abstract
Objectives This study aimed to evaluate the feasibility and efficacy of pressure-temperature sensor–tipped wire–derived coronary flow capacity (PTW-CFC) for assessing flow impairment and prognosis.
Background CFC provides an integrated coronary physiological assessment in which coronary flow reserve and coronary flow during hyperemia are organized.
Methods A total of 643 native de novo lesions for which physiological assessments were performed using a PressureWire (St. Jude Medical, St. Paul, Minnesota) in patients with stable coronary artery disease were identified. The entire cohort was stratified by PTW-CFC according to the well-validated thresholds of coronary flow reserve and the corresponding inverse of thermodilution-derived mean transit time under hyperemia. Coronary physiological indices and the prevalence of major adverse cardiac events (MACE) were assessed according to PTW-CFC categories. Furthermore, in patients who underwent percutaneous coronary intervention (PCI), post-PCI PTW-CFC categorization was performed and clinical outcomes were evaluated.
Results PTW-CFC categorization efficiently discriminated previously validated coronary physiological parameters for functional stenosis severity and microvascular dysfunction. MACE rates during follow-up (2.4 years) were significantly associated with advanced impairment of PTW-CFC except for severely reduced PTW-CFC. In the subgroup analysis of patients with severely reduced pre-PCI PTW-CFC who underwent successful PCI, MACE incidence was significantly frequent in patients with post-PCI non-normal PTW-CFC compared with those with post-PCI normal PTW-CFC.
Conclusions PTW-CFC mapping was feasible, provided accurate stratifications of coronary flow impairment, and may predict MACE. Combined analysis involving PTW-CFC and fractional flow reserve may enrich the clinical implication of integrated coronary physiology and may help predict prognosis.
Fractional flow reserve (FFR) is an extensively investigated surrogate for impairment of coronary blood flow that reflects the physiological severity in epicardial coronary artery disease (CAD). Although the measurement is highly feasible, FFR could not determine the extent of microvascular dysfunction that occurs irrespective of epicardial stenosis. A comprehensive diagnostic approach toward CAD is warranted based on prior evidence indicating a strong link between adverse clinical outcomes and microcirculatory disturbance as well as epicardial flow impairment (1). Coronary flow reserve (CFR) indicates integrated coronary vascular function, which is known to be associated with adverse cardiac events (2,3). The problems in use of CFR lie in the unstable baseline hemodynamics, attenuated hyperemic responses caused by caffeine or other potential conditions, and heterogeneous population of low CFR, which includes patients with high coronary flow at baseline, limited flow at hyperemia, or impaired vasodilatory response to adenosine (4).
To overcome the limitations of CFR, the concept of coronary flow capacity (CFC) has been introduced, which integrates CFR with hyperemia coronary flow into a comprehensive platform of coronary flow characteristics (5). CFC was first developed using noninvasive positron emission tomography (PET) and was subsequently verified using an invasive intracoronary Doppler flow wire (5,6). Adding to the strong theoretical fundamentals of CFC, these validations are important for potential clinical use, for the prognostic implication could be better than CFR alone (6). However, PET availability is still limited, and Doppler flow velocity measurement is distinctively challenging and time-consuming. The present study investigated the diagnostic and prognostic efficacy of CFC obtained using pressure-temperature sensor–tipped wire (PTW), which is likely to be technically feasible for obtaining appropriate physiological data compared with intracoronary Doppler crystal-equipped guidewires. Furthermore, FFR can be determined together with CFC by the same PTW. We hypothesized that PTW-CFC could provide a platform for hemodynamics assessments and prediction of clinical outcomes, which would enrich the understanding in comprehensive coronary physiology combined with simultaneous FFR assessment.
Methods
Patient population
From January 2011 to March 2017, patients with known or suspected CAD who underwent coronary physiological assessments using PressureWire (St. Jude Medical, St. Paul, Minnesota) at Tsuchiura Kyodo General Hospital were identified from the institutional database. A physiological study was indicated for vessels with intermediate coronary lesions (30% to 80% diameter stenosis on visual assessment). In the presence of multiple coronary stenoses, a single vessel with the most severely decreased FFR value was used for the present analysis. Patients with indications for revascularization of ≥2 branches were excluded. This study protocol excluded patients with angiographically significant left main disease, previous coronary artery bypass surgery, renal insufficiency with baseline creatinine >2.0 mg/dl, presence of unstable symptoms (worsening angina or rest angina within 1 month), myocardial infarction (MI) episode within 30 days before CAG, decompensated heart failure, cardiogenic shock, arrhythmia including atrial fibrillation, extremely tortuous or calcified coronary arteries, and vessels with visible collateral development or ostial stenosis. For patients treated with subsequent successful PCI and physiological examinations performed both pre- and post-PCI, subgroup analyses were performed to determine the implications of change in CFC categories following PCI. Successful PCI was defined as post-PCI Thrombolysis In Myocardial Infarction flow grade ≥3, no side branch occlusion or distal embolization, and no PCI-related MI according to current guidelines (7). The institutional ethics committee approved the study protocol. Before catheterization, all patients provided written informed consent for enrollment in the institutional database for potential future investigations. All patient data and procedural details were obtained from medical records.
Catheterization and physiological studies using thermodilution methods
Each patient underwent standard CAG via the radial artery with a 5-F system, and PCI with a 6-F system. Revascularization was indicated based on patient symptoms as well as noninvasive test results and FFR values. Successful PCI was performed in 99% of the patients; 3 patients who suffered from PCI-related MI were not included (7). Quantitative coronary angiography analyses were performed using dedicated offline software (QAngio XA 7.3; Medis, Leiden, the Netherlands). Physiological parameters including FFR, CFR, and mean transit time (Tmn) were obtained using a single 0.014-inch PressureWire (8). After wire calibration, the intracoronary pressure distal to the coronary stenosis was measured. Subsequently, 3 ml of room-temperature saline was administered 3 times, and the baseline Tmn was determined. For both measurements, maximal hyperemia was induced by intravenous infusion of adenosine 5ʹ-triphosphate (160 μg·kg−1·min−1). FFR was calculated as the ratio of mean distal-to-aortic coronary pressure during maximum hyperemia. CFR was defined as resting Tmn divided by hyperemic Tmn. The index of microvascular resistance (IMR) was defined as Pd × Tmn or Pa × Tmn × ([1.35 × ratio of mean distal-to-aortic coronary pressure] −0.32) during hyperemia (9).
Derivation of CFC map
According to the CFC concept derived from PET or Doppler flow velocity, PTW-CFC categorized lesions into 4 ranges using CFR and the inverse of hyperemic Tmn (5,6). As shorter Tmn suggests higher coronary flow velocity, 1/hyperemic Tmn is the concept that correlates with absolute coronary blood flow during hyperemia (10,11). Because the thresholds of 1/Tmn have not been well documented, they were matched according to the percentiles corresponding to CFR as follows: normal PTW-CFC, indicating no myocardial ischemia, CFR ≥2.80 with corresponding 1/Tmn ≥3.70 (45th percentile) (12); mildly reduced PTW-CFC, CFR <2.80 and ≥2.10, which were the reported upper limits for inducible ischemia, and corresponding 1/Tmn <3.70 and ≥2.56 (65th percentile each) (13); moderately reduced PTW-CFC, CFR <2.10 and ≥1.70, which reflected lower limits for inducible ischemia, and 1/Tmn <2.56 and ≥2.00 (77th percentile each) (13); and severely reduced PTW-CFC, definite ischemia, CFR <1.70, and 1/Tmn <2.00 (14).
Clinical follow-up
Clinical follow-up data were collected via a review of the medical records or telephone interviews. Spontaneous MI was diagnosed based on the third universal definition of MI (7). Clinically driven revascularization was applied to revascularization of any vessels occurred at least 3 months after the index CAG. All revascularizations required or scheduled based on the index CAG results were performed within 3 months after the procedures. Major adverse cardiac events (MACE) were defined as a composite of death from cardiac cause, nonfatal spontaneous MI, hospital admission due to congestive heart failure (CHF), and clinically driven revascularization. Although obstructive CAD is classically linked to MI and revascularization, we included CHF hospitalization as an endpoint because CFR reflects integrated coronary vascular function that is not restricted to epicardial stenosis and could highlight microvascular dysfunction or diastolic load (15,16).
Statistical analysis
Categorical data, expressed as frequencies and percentages, were compared using the chi-square test or Fisher’s exact test, as appropriate. Normality of the variances was tested using Shapiro-Wilk tests. Continuous biochemical or physiological data were expressed as median (interquartile range [IQR]) and analyzed using the Mann-Whitney test or Kruskal-Wallis test for variables with non-normal distribution, or analysis of variance for those with normal distribution. Analyses of linear trends across PTW-CFC categories were performed using the Jonckheere-Terpstra trend test. Event rates over time were estimated using the Kaplan-Meier method, and linear trends were tested with log-rank tests. A Cox proportional hazards regression model was used to identify independent predictors of MACE. The covariates used in multivariate analysis were selected with the criterion of p < 0.15 in the univariate analysis, and normal PTW-CFC was used as a reference for the other PTW-CFC categories. A collinearity index was used for checking linear combinations among covariates, and the Akaike information criterion for avoiding overfitting. All statistical analyses were performed using JMP 11.2.0 (SAS Institute Inc., Cary, North Carolina). Two-sided p < 0.05 was considered statistically significant.
Results
Baseline clinical features and physiological parameters of the total cohort
Of 695 lesions transferred to the institutional imaging and physiological laboratory that independently analyzed data, 23 (3.3%) with suboptimal recordings of physiological indices including pressure drift, and 29 (4.2%) with ineligible coronary hemodynamic status were excluded. Therefore, a total of 643 patients with 643 lesions were included in the present analysis. Median FFR and CFR values were 0.81 (IQR: 0.74 to 0.87) and 2.65 (IQR: 1.78 to 3.70), respectively. We created the PTW-CFC map using CFR and the inverse of hyperemic Tmn, and the patients were categorized into 4 PTW-CFC categories (Figure 1). Normal, mildly reduced, moderately reduced, and severely reduced PTW-CFC categories consisted of 408 (63.4%), 97 (15.1%), 63 (9.8%), and 75 (11.7%) vessels, respectively. The baseline clinical characteristics and physiological parameters of each PTW-CFC group are summarized in Table 1. There were no significant differences in patient demographics. The angiographic stenosis and physiological properties of the lesions were significantly stratified according to PTW-CFC. The frequency of abnormal values of FFR ≤0.80 and CFR <2.00, and the ratio of angiographic nonsignificant CAD defined as diameter stenosis <50% were also clearly stratified across PTW-CFC categories (all p values <0.001). Furthermore, there were significant differences in baseline Tmn, especially between the normal or mildly reduced PTW-CFC groups (0.79 [IQR: 0.51 to 1.18] and 0.82 [IQR: 0.66 to 1.11], respectively) and moderately or severely reduced PTW-CFC groups (0.97 [IQR: 0.65 to 1.46] and 0.98 [IQR: 0.86 to 1.36], respectively). Revascularization was performed in 195 (47.8%), 46 (47.4%), 46 (73.0%), and 62 (82.7%) patients according to PTW-CFC categories, respectively. Notably, 13 patients with severely reduced PTW-CFC (17.3%) for whom PCI was deferred were characterized by high IMR values (median: 42.9; IQR: 34.5 to 67.0), indicative of microvascular dysfunction as a primary cause of flow impairment.
PTW-CFC Map
The distribution of 643 vessels across the 2-dimensional map of coronary flow reserve (CFR) versus the inverse of hyperemic mean transit time (Tmn) with 4 meaningful categories. (A) A total of 408 vessels (63.5%) had normal pressure-temperature sensor–tipped wire–derived coronary flow capacity (PTW-CFC), (B) 97 (15.1%) patients had mildly reduced PTW-CFC, (C) 63 (9.8%) patients had moderately reduced PTW-CFC, and (D) 75 (11.7%) patients had severely reduced PTW-CFC.
Baseline Patient Characteristics Based on PTW-CFC Categories
Figure 2 shows the distribution of vessels divided by the combination of FFR and CFR thresholds (0.80 and 2.00, respectively) across PTW-CFC categories. Eighteen (28.6%) vessels with moderately reduced PTW-CFC were FFR >0.80 and CFR <2.00, which are known to have poor prognoses but not indicated for revascularization (17). The majority of severely reduced PTW-CFC group (74.7%) were classified into diseased vessels with FFR ≤0.80 and CFR <2.00, the part of which may benefit from the revascularization.
Distribution of Vessels Divided by Combination of FFR and CFR Across the PTW-CFC Categories
The number of vessels divided by the combined thresholds of fractional flow reserve (FFR) of 0.80 and coronary flow reserve (CFR) of 2.00 in each PTW-CFC group. Values are n (percent of each row). Abbreviations as in Figure 1.
Clinical outcomes
The median follow-up period was 2.4 years (IQR: 1.1 to 4.0 years), during which 4 patients experienced nonfatal MI, 3 patients died of cardiovascular causes, 10 patients required hospital admission due to worsening CHF, and 50 patients needed revascularization (overall MACE rate: 67 of 643 [10.4%]). MACE rate in each PTW-CFC stratum was shown in Online Table 1. Figure 3 shows Kaplan-Meier curves showing survival from MACE according to PTW-CFC categories. MACE incidence significantly increased along with advanced impairment of PTW-CFC except for severely reduced CFC group (p = 0.002). The severely reduced PTW-CFC group, in which 62 of 75 patients (82.7%) were treated with PCI, showed clinical outcomes comparable to those of the composite of other groups (p = 0.86). Clinically driven revascularization based on the index CAG was performed in 349 (54.3%) patients, and MACE rate in the PCI cohort was 48 of 349 (13.8%) (Online Table 1). The survival from MACE was also significantly stratified across PTW-CFC categories in patients who underwent PCI and those who deferred (Figure 4) (p = 0.041 and 0.044, respectively). Worst prognosis was noted in the moderately reduced PTW-CFC group compared with other categories in the PCI cohort, possibly due to outweighed risk compared with benefit by PCI. Normal PTW-CFC group had favorable clinical outcomes in the deferred population. No adverse events were documented in patients with severely reduced CFC (n = 13), possibly due to underpowered nature of this analysis.
MACE Incidence According to PTW-CFC Categories
Kaplan-Meier curves demonstrating the survival from major adverse cardiac events (MACE) in patients with (A) normal, (B) mildly reduced, (C) moderately reduced, or (D) severely reduced PTW-CFC in the investigated coronary arteries. The PTW-CFC categorization significantly discriminated the incidence of MACE (p = 0.002). Abbreviations as in Figure 1.
Survival From MACE in Patients Across PTW-CFC Strata in PCI Cohort and Deferred Cohort
Kaplan-Meier curves showing the survival from MACE in patients (A) who underwent percutaneous coronary intervention (PCI) and (B) who deferred. Patients were divided into (A) normal, (B) mildly reduced, (C) moderately reduced, or (D) severely reduced PTW-CFC in the investigated coronary arteries. Severely reduced PTW-CFC was removed from the deferred cohort because no MACE was documented. In both cohorts, the PTW-CFC categorization significantly discriminated the incidence of MACE (p = 0.041 and 0.044, respectively). Abbreviations as in Figures 1 and 3.
Univariate Cox proportional analyses revealed that diameter stenosis <50%, FFR, CFR, and PTW-CFC were significantly associated with the incidence of MACE (Table 2). In a multivariate model, moderately reduced PTW-CFC (hazard ratio [HR]: 2.273; 95% confidence interval [CI]: 1.051 to 4.941; p = 0.037), FFR (HR: 0.075; 95% CI: 0.006 to 0.875; p = 0.039), and dyslipidemia (HR: 1.751; 95% CI: 1.034 to 3.086; p = 0.037) were the independent predictors for MACE.
Independent Predictors for MACE
Change in PTW-CFC categories following PCI and the impact on MACE incidence in the pre-PCI severely reduced PTW-CFC population
We performed a subgroup analysis in 230 vessels with FFR ≤0.80 of 230 patients who underwent successful PCI and optimal physiological assessments before and after intervention. Median FFR and CFR values were 0.73 (IQR: 0.64 to 0.77) and 2.27 (IQR: 1.52 to 3.18) at baseline, and 0.87 (IQR: 0.84 to 0.92) and 3.33 (IQR: 2.09 to 5.21) after PCI, respectively. All patients demonstrated FFR improvement following PCI, whereas CFR and Tmn during maximum hyperemia did not improve in 61 (26.5%) and 47 (20.4%) territories, respectively. Although pre-PCI FFR values were efficiently stratified, post-PCI FFR values were not significantly different across the PTW-CFC categories (p = 0.20). Patient demographics and changes in the physiological parameters following PCI in each PTW-CFC category are summarized in Online Table 2.
Table 3 summarizes the changes in PTW-CFC categories following PCI. PTW-CFC categories were generally improved by revascularization; normal, mildly reduced, moderately reduced, and severely reduced PTW-CFC categories were assigned to 115 (50.0%), 38 (16.5%), 29 (12.6%), and 48 (20.1%) vessels at baseline, and 182 (79.1%), 28 (12.1%), 10 (4.3%), and 10 (4.3%) vessels after PCI, respectively. MACE was documented in 30 patients (13.0%). The incidence of MACE was not significantly different across post-PCI PTW-CFC (Online Figure 1).
Changes in PTW-CFC Categories Following PCI
In vessels with pre-PCI severely reduced PTW-CFC (n = 48), 29 (60.4%) cases exhibited drastic CFC improvement to normal PTW-CFC after PCI. The incidence of MACE was significantly lower in this subgroup compared with cases without the improvement (i.e., post-PCI non-normal PTW-CFC) (Figure 5). Relatively favorable clinical outcomes of the severely reduced PTW-CFC group of the total cohort could be partially attributed to the dominant prevalence of the post-PCI normal PTW-CFC population. Online Table 3 shows a comparison of physiological parameters obtained before and after PCI between the groups with or without improvement. Although there were no significant differences in the baseline physiological parameters, pre-PCI FFR values were lower in the post-PCI normal PTW-CFC group. CFR and IMR were more drastically improved in the post-PCI normal PTW-CFC group compared with the other group.
MACE Incidence in Patients With Pre-PCI Severely Reduced PTW-CFC Divided According to the Improvement Following PCI
Kaplan-Meier curves showing survival after MACE in subgroups of patients with severely reduced PTW-CFC before PCI. The incidence of MACE was significantly lower in (A) cases that exhibited drastic CFC improvement to normal PTW-CFC following PCI compared with (B) those cases with post-PCI mildly, moderately, or severely reduced PTW-CFC (p = 0.027). Abbreviations as in Figures 1, 3, and 4.
Discussion
This is the first study validating the prognostic and diagnostic efficacy of CFC concept obtained using PTW, which provided a simultaneous FFR assessment. The present study provides the following novel findings: 1) the CFC map was successfully obtained using PTW-derived CFR and hyperemic Tmn; 2) the CFC categorization could stratify physiological properties; 3) the CFC categorization could discriminate MACE incidences except for severely reduced PTW-CFC group; 4) the MACE incidence was prominently lower in cases of post-PCI normal PTW-CFC re-categorized from pre-PCI severely reduced PTW-CFC; and 5) PCI may modify the PTW-CFC–based prognosis of patients with severely reduced PTW-CFC.
Important limitations of CFR lie in its difficulty in differentiating epicardial stenosis, diffuse artery disease, and microvascular dysfunction, and its relatively greater dependence on resting hemodynamic status. Johnson and Gould (5) first proposed the concept of CFC, relying on the rationale that the combination of CFR with hyperemic flow comprehensively captures all relevant flow characteristics of the interrogated vasculature. To date, clinical usefulness of the CFC concept obtained by PET and invasive Doppler flow velocity techniques have been confirmed, yet the applicability and practical usage remain low. A prior multicenter trial reported that FFR and thermodilution-derived CFR could be obtained in 100% and 97% of patients with CAD, respectively, whereas an optimal Doppler-derived CFR could be obtained only in 69% (18). In addition, flow velocity measurements require meticulous sampling to ensure that the optimal flow velocity envelope is obtained. The present study has successfully validated the CFC concept obtained using PressureWire, which has been routinely used for FFR measurements worldwide with high feasibility.
Van de Hoef et al. (6) documented the physiological complementarity of hyperemic flow and CFR on the basis of the CFC concept, which translates into improved discrimination of patients at risk for MACE compared with CFR alone. In accordance, we documented the efficacy of MACE discrimination by PTW-CFC categorization. Worse prognoses in the moderately reduced PTW-CFC group may be driven by the prevalent microvascular dysfunction, described as high IMR in PCI deferred population, and outweighed PCI-related risk over the benefit in patients indicated for PCI (19). Importantly, a multivariate model revealed the independent contribution of FFR and PTW-CFC on the prediction of MACE. Combined use of CFC and FFR obtained using a single wire may discriminate diverse causes of CAD in terms of flow impairment, including microcirculatory dysfunction and epicardial focal or diffuse atherosclerosis; thus, each could be incrementally linked to clinical outcomes. A relatively favorable prognosis in the severely reduced CFC group observed in the present study appears to go against “biological gradient” Bradford Hill criteria, whereas we might be able to make a hypothesis that PCI provides a potentially greater benefit of revascularization in this group due to the modification of the anticipated multiple worse physiological profiles.
Previous clinical trials have hardly demonstrated the benefits of PCI in terms of lowering long-term adverse events over optimal medical therapy alone (20). The DEFER (deferral of percutaneous coronary intervention) trial showed that deferral of PCI for vessels with FFR ≥0.75 was associated with favorable outcomes during 15-year follow-up (21). Notably, we believe the present study implicated the potential targets whose clinical outcomes could be preferably modified by PCI. Although the severely reduced PTW-CFC group had the worst physiological profile, the MACE incidence was comparable to those of the other groups combined. A majority of cases with severely reduced PTW-CFC demonstrated drastic CFC improvement to normal PTW-CFC following PCI; this subgroup had favorable clinical outcomes that might have preferably modified the anticipated poor clinical outcomes of severely reduced PTW-CFC group as a whole. Although no direct evidence could underscore the mechanisms, only the cases of severely reduced PTW-CFC at baseline could demonstrate a prominent improvement in coronary flow, which could not be determined solely by FFR. Of note, the indication for PCI was based on FFR values ≤0.80; therefore, the combined use of CFC categorization and FFR measured using PTW could determine patients who could benefit from PCI. In addition, because the relatively large population with FFR >0.80 and CFR <2.00 in the moderately reduced PTW-CFC group could result in an increased incidence of MACE, PCI was not indicated, thus leading to the overall worst clinical outcomes. Conversely, patients with better PTW-CFC might not benefit from PCI even if they have FFR ≤0.80, as implicated in previous reports (22). Larger prospective studies are warranted to clarify the potential utility of PTW-CFC categorization with simultaneous FFR assessment that was suggested by this hypothesis-generating study.
Study limitations
Because this study was an observational study at a single center, it cannot escape selection bias. With no established cutoff values for hyperemic Tmn, the proposed cutoff values were derived from the percentiles of hyperemic Tmn corresponding to CFR cutoffs defined by the present population. The coronary thermodilution technique used in the present study could partially overestimate the value of CFR due to its methodological limitations. This method could be influenced by the amount of perfused myocardial mass, which is not the case in PET or Doppler flow velocity technique. Although a recent study shows the association of the perfused amount of myocardium with IMR, the relationship is modest, and it is not likely that prognostic results in the present study were attributed to the subtended myocardial mass of each group because IMR was not used for the categorization (23). However, the interpretation of our results needs caution because the categorization is based on CFR and the absolute value of hyperemic Tmn, which was obtained on the basis of thermodilution method. Further insight into the impact of subtended myocardial mass on PTW-derived physiological indices is warranted.
A telephone survey to collect long-term follow-up data could have been exposed to patient recall bias, which may have resulted in an underestimation of MACE incidence. No MACE was confirmed in patients with severely reduced PTW-CFC who deferred PCI (0 of 13), possibly due to underpowered nature of the analysis, because the population was presumed to have poor clinical outcomes because of the high IMR levels (24). The present data could not demonstrate improvements in MACE discrimination by the physiological complementarity of hyperemic flow and CFR, as shown in the previous study using Doppler crystal–equipped guidewire-derived CFC, although the improvements had little implication in CFC categorization (6). Nevertheless, the present PTW-CFC concept not only discriminated the patient outcomes but also provided an informative platform for physiological characteristics and for predicting benefits of revascularization with high feasibility.
Conclusions
PTW-CFC mapping was feasible and provided accurate predictions of coronary flow impairment, and categorization was associated with the incidence of MACE independently with FFR. Profiles of severely reduced PTW-CFC combined with FFR ≤0.80 may specify the subset of patients who could achieve potentially improved clinical outcomes with PCI. PTW-CFC, which is complementary to FFR and can be obtained without meticulous handling, may enrich the clinical implication of integrated coronary physiology and help predict prognosis.
WHAT IS KNOWN? CFC provides an integrated coronary physiological assessment in which coronary flow reserve and coronary flow during hyperemia are integrated. Clinical utilities of CFC have been confirmed in Doppler-flow wire and PET.
WHAT IS NEW? PFW-CFC, which could be obtained simultaneously with FFR, provides stratification of physiological indices and is associated with MACE independently of FFR.
WHAT IS NEXT? Larger prospective studies are warranted to clarify the potential utility of PTW-CFC categorization, especially in the identification of patients who may benefit from revascularization.
Acknowledgments
The authors thank all the physicians, nurses, other catheter laboratory staff members, and patients involved in this study. The authors especially thank Mr. Tatsuhiko Kuramochi for assistance with the statistical analysis, and Ms. Noriko Terada and Mr. Manabu Otomo for their technical assistance with their fields of expertise.
Appendix
Footnotes
The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- CAD
- coronary artery disease
- CAG
- coronary angiography
- CFC
- coronary flow capacity
- CFR
- coronary flow reserve
- CHF
- congestive heart failure
- FFR
- fractional flow reserve
- IMR
- index of microvascular resistance
- MACE
- major adverse cardiac event(s)
- PCI
- percutaneous coronary intervention
- PET
- positron emission tomography
- PTW
- pressure-temperature sensor–tipped wire
- Tmn
- mean transit time
- Received October 9, 2017.
- Revision received December 21, 2017.
- Accepted January 2, 2018.
- 2018 American College of Cardiology Foundation
