Abstract
Background:
Little evidence is available regarding the long-term outcome in elderly patients after deferral of revascularization based on fractional flow reserve (FFR).
Methods and Results:
From the J-CONFIRM registry (long-term outcomes of Japanese patients with deferral of coronary intervention based on fractional flow reserve in multicenter registry), 1,262 patients were divided into 2 groups according to age: elderly and younger patients (aged ≥75 or <75 years, respectively). The primary endpoint was the cumulative 5-year incidence of target vessel failure (TVF), defined as a composite of cardiac death, target vessel-related myocardial infarction (TVMI), and clinically driven target vessel revascularization (CDTVR). Cumulative 5-year incidence of TVF was not significantly different between elderly and younger patients (14.3% vs. 10.8%, P=0.12). Cardiac death occurred more frequently in elderly patients than younger patients (4.4% vs. 0.8%, P<0.001), whereas TVMI and CDTVR did not differ between groups (1.3% vs. 0.9%, P=0.80; 10.7% vs. 10.1%, P=0.80, respectively). FFR values in lesions with diameter stenosis <50% were significantly higher in elderly patients than in younger patients (0.88±0.07 vs. 0.85±0.07, P=0.01), whereas this relationship was not observed in those with diameter stenosis ≥50%.
Conclusions:
Elderly patients had no excess risk of ischemic events related to the deferred coronary lesions by FFR, although FFR values in mild coronary artery stenosis were modestly different between elderly and younger patients.
Fractional flow reserve (FFR) is the standard invasive method used to evaluate the functional significance of epicardial coronary artery stenosis.1
The safety of FFR-guided deferral of revascularization has been reported in previous randomized controlled trials and observational studies.2–5
Recently, the J-CONFIRM registry (long-term outcomes of Japanese patients with deferral of coronary intervention based on fractional flow reserve in multicenter registry) has reported the low incidence of target vessel failure (TVF) after deferral of revascularization based on FFR among patients with chronic coronary syndrome (CCS), highlighting the safety of FFR-based deferral of revascularization in real-world practice.6,7
Editorial p ????
Elderly patients are more dominant in the CCS population and often present with atypical symptoms than younger patients; therefore, assessing myocardial ischemia should be encouraged in elderly patients. Previous studies have consistently demonstrated that elderly patients have higher FFR values than younger patients despite a similar degree of coronary stenosis8–10
due to several potential mechanisms, such as a loss of functional cardiomyocytes, microvascular dysfunction resulting from long-standing hypertension and diastolic dysfunction,11,12
and a decreased response to vasodilator drugs.13
Although these findings could potentially affect FFR-guided decision-making for elderly patients, little data exist on long-term outcomes in elderly patients after FFR-based deferral of coronary revascularization. Further, the impact of age on FFR values has not been thoroughly investigated in a large-scale study (i.e., n>1,000).8–10
In the present study, we aimed to evaluate the long-term prognosis of elderly patients with deferred revascularization guided by FFR and the impact of age on the FFR values by analyzing the J-CONFIRM registry.
Methods
Study Design and Population
This study was a sub-analysis of the J-CONFIRM registry, a prospective multicenter registry investigating clinical outcomes in Japanese patients with deferral of revascularization based on FFR at 28 Japanese centers (Supplementary Appendix) between September 2013 and June 2015.6
Briefly, this registry prospectively included 1,263 patients with 1,447 angiographically intermediate coronary artery stenosis in whom revascularization was deferred based on FFR. Key exclusion criteria were acute myocardial infarction, cardiogenic shock, chronic total occlusion, a graft lesion, or limited life expectancy. For the present study, patients were divided into 2 groups based on age <75 or ≥75 years. Also, to assess the impact of age on FFR values in sub-groups with a similar degree of coronary stenosis, patients were classified into 2 groups according to age and angiographic diameter stenosis (DS).
All patients gave written informed consent for the procedure and follow-up protocol, which was approved by the local ethics committee at all participating centers and was in accordance with the Declaration of Helsinki. The research was funded by an unrestricted grant from Abbott Medical Japan, Phillips Japan, and Boston Scientific Japan, which had no oversight or input on data gathering, data interpretation, or the preparation of this manuscript. This study was registered with http://www.umin.ac.jp, unique identifier UMIN000014473.
Data Collection and Follow-up
All baseline and follow-up data were prospectively collected from the medical records or by telephone contacts with the patients, relatives, and referring physicians at discharge, 1-, 2-, 3-, 4-, and 5-year follow ups by each site investigator. All clinical events were adjudicated by an independent clinical events committee.
Angiographic Analyses and FFR Measurements
Quantitative and qualitative coronary angiographic analyses were performed in a core laboratory (ENDOCORE, Fukuoka, Japan) by independent analysts blinded to the clinical information.6
The details of quantitative coronary angiography analysis have been previously reported.6
FFR was measured with a commercially available coronary pressure wire (Pressure Wire Certus, St Jude Medical, St Paul, AK; Prestige, Volcano Ltd, Cordova, CA, USA). After administration of intracoronary nitrates, the pressure wire was positioned at the distal segment of a target lesion. Maximum hyperemia was induced by intravenous infusion of adenosine (150–180 μg) via the forearm or femoral vein or intracoronary injection of adenosine (40–80 μg), papaverine (8–12 mg), or nicorandil (2 mg). FFR was calculated as the ratio of the mean distal coronary pressure to the mean aortic pressure during maximum hyperemia.
Clinical Endpoints and Definitions
The primary study endpoint was 5-year TVF, defined as a composite of cardiac death, target vessel-related myocardial infarction (TVMI), and clinically driven target vessel revascularization (CDTVR). Secondary endpoints were major adverse cardiovascular events (MACE), defined as a composite of all-cause death, TVMI, and CDTVR. Death was regarded as cardiac death unless other non-cardiac causes could be identified. Myocardial infarction was defined according to the Academic Research Consortium definition.14
Revascularization was considered clinically indicated if: (1) the angiographic percentage DS of the target lesion was ≥50% by qualitative coronary angiographic assessment, in the presence of ischemic signs or symptoms; or (2) the DS was ≥70% by qualitative coronary angiographic assessment, irrespective of ischemic signs or symptoms.13
Statistical Analysis
Categorical variables are shown as absolute values and percentages and were analyzed using Fisher’s exact test. Continuous variables are expressed as mean±SD and were analyzed using the Student’s t-test. Kaplan-Meier cumulative event curves were constructed for time-to-event variables and compared using the log-rank test. Cox regression analysis was performed to evaluate the prognostic significance of age (<75 or ≥75 years) for TVF, MACE and CDTVR. Age was adjusted by clinically important variables including diabetes mellitus, dyslipidemia, FFR value (continuous), hemodialysis, hypertension, left main coronary artery lesion, lesion length (≥20-mm or not), male gender, moderately to severely calcified lesion, angiographic DS (≥50% or not), previous peripheral artery disease, and previous percutaneous coronary intervention.6
Although our analysis was based on a cause-specific hazard by treating all-cause or non-cardiac death as censoring, competing-risk subdistribution analysis had negligible effect on all estimates (e.g., change in 5-year incidence estimate of CDTVR was <0.7% in the elderly group). Statistical analyses were performed with SPSS 27 (IBM, Armonk, NY, USA). All statistical analyses were 2-tailed. P values <0.05 were considered statistically significant.
Results
Study Population
Of 1,263 patients, 1,262 were analyzed for the current study (Figure 1). Five-year clinical follow-up was completed in 92.2% of patients. Patient and lesion characteristics are summarized in
Tables 1
and
2. Elderly patients were more likely to be female and had more comorbidities with greater lesion complexities.
Table 1.
Patient Characteristics
| |
<75 years
(n=829) |
≥75 years
(n=433) |
P value |
| Age, years |
65.1±7.8 |
80.0±3.7 |
<0.001 |
| Male |
658 (79.4) |
281 (65.0) |
<0.001 |
| Hypertension |
626 (75.5) |
342 (79.0) |
0.17 |
| Dyslipidemia |
554 (66.8) |
254 (58.7) |
0.004 |
| Diabetes mellitus |
328 (39.6) |
151 (34.9) |
0.10 |
| Current smoking |
300 (36.2) |
103 (23.8) |
<0.001 |
| Dialysis |
48 (5.8) |
17 (3.9) |
0.16 |
| Previous myocardial infarction |
257 (31.0) |
108 (24.9) |
0.02 |
| Previous PCI |
496 (59.8) |
251 (58.0) |
0.52 |
| Previous CABG |
16 (1.9) |
16 (3.7) |
0.06 |
| Previous heart failure |
58 (7.0) |
51 (11.8) |
0.004 |
| Previous cerebrovascular disease |
64 (7.7) |
56 (12.9) |
0.003 |
| Previous peripheral artery disease |
80 (9.7) |
74 (17.1) |
<0.001 |
| Clinical symptoms |
|
|
0.69 |
| Asymptomatic |
425 (51.3) |
224 (51.7) |
|
| CCS I |
294 (35.5) |
160 (37.0) |
|
| CCS II |
79 (9.5) |
38 (8.8) |
|
| CCS III |
15 (1.8) |
7 (1.6) |
|
| CCS IV |
16 (1.9) |
4 (0.9) |
|
| eGFR, mL/min/m2 |
55.5±24.8 |
53.5±23.6 |
0.18 |
| HbA1c, % |
6.3±1.0 |
6.1±0.9 |
0.007 |
| LDL-C, mg/dL |
100.7±31.9 |
98.0±29.4 |
0.17 |
| LVEF, % |
62.5±11.8 |
63.0±13.1 |
0.54 |
| Medication at discharge |
|
|
|
| Antiplatelet therapy |
662 (79.9) |
339 (78.3) |
0.52 |
| Anticoagulants |
58 (7.0) |
46 (10.6) |
0.03 |
| Calcium channel blocker |
419 (50.5) |
236 (54.5) |
0.18 |
| ACE-I/ARB |
476 (57.4) |
256 (59.1) |
0.56 |
| β-blocker |
291 (35.1) |
129 (29.8) |
0.06 |
| Statin |
549 (66.2) |
267 (61.7) |
0.11 |
| FFR value† |
0.85±0.06 |
0.86±0.07 |
0.06 |
| FFR category† |
|
|
0.27 |
| <0.76 |
32 (3.9) |
14 (3.2) |
|
| 0.76–0.80 |
121 (14.6) |
47 (10.9) |
|
| 0.81–0.85 |
299 (36.1) |
152 (35.1) |
|
| 0.86–0.90 |
212 (25.6) |
121 (27.9) |
|
| 0.91–1.00 |
165 (19.9) |
99 (22.9) |
|
Data are presented as n (%) or mean±SD. †The lowest FFR value was used for analysis if a patient had ≥2 lesions with FFR measurements. ACE-I, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; CABG, coronary artery bypass graft; CCS, Canadian cardiovascular society; eGFR, estimated glomerular filtration rate; FFR, fractional flow reserve; HbA1c, hemoglobin A1c; LDL-C, low-density lipoprotein cholesterol; LVEF, left ventricular ejection fraction; PCI, percutaneous coronary intervention.
Table 2.
Lesion Characteristics
| |
<75 years
(n=956) |
≥75 years
(n=490) |
P value |
| Target vessel |
| LMCA |
24 (2.5) |
13 (2.7) |
0.87 |
| LAD |
461 (48.2) |
242 (49.4) |
0.68 |
| LCX |
219 (22.9) |
108 (22.0) |
0.71 |
| RCA |
253 (26.5) |
131 (26.7) |
0.91 |
| ACC/AHA lesion classification |
|
|
0.07 |
| A |
123 (12.9) |
40 (8.0) |
|
| B1 |
272 (28.5) |
137 (28.0) |
|
| B2 |
388 (40.6) |
208 (42.4) |
|
| C |
171 (17.9) |
104 (21.2) |
|
| In-stent restenosis |
64 (6.7) |
41 (8.4) |
0.25 |
| Tortuous vessel |
146 (16.9) |
99 (21.7) |
0.03 |
| Calcification |
98 (11.3) |
87 (19.1) |
<0.001 |
| Bifurcation |
257 (29.7) |
152 (33.3) |
0.17 |
| Qualitative coronary angiography analysis† |
| RVD, mm |
2.8±0.7 |
2.8±0.6 |
0.90 |
| <2.5 mm |
309 (36.2) |
135 (30.1) |
0.03 |
| MLD, mm |
1.6±0.4 |
1.6±0.5 |
0.90 |
| Diameter stenosis, % |
43.0±11.5 |
43.4±11.6 |
0.50 |
| ≥50% |
248 (29.1) |
132 (29.5) |
0.90 |
| Lesion length, mm |
13.0±5.7 |
13.3±6.6 |
0.47 |
| ≥20 mm |
69 (8.0) |
50 (11.0) |
0.07 |
Data are presented as n (%) or mean±SD. †Data on qualitative coronary angiography analysis were available in 853 and 448 lesions of the <75 and ≥75 years groups, respectively. LAD, left anterior descending; LCX, left circumflex; LMCA, left main coronary artery; MLD, minimum lumen diameter; RCA, right coronary artery; RVD, reference vessel diameter.
Five-year clinical outcomes are summarized in
Table 3
and
Figure 2. There was no significant difference in TVF between 2 groups (14.3% vs. 10.8%, P=0.12). Elderly patients had a higher incidence of MACE (28.0% vs. 14.4%, P<0.001), all-cause death (19.8% vs. 4.6%, P<0.001), cardiac death (4.4% vs. 0.8%, P<0.001), and non-cardiac death (16.1% vs. 3.9%, P<0.001) than younger patients, whereas there were no significant differences in TVMI (1.3% vs. 0.90%, P=0.80), clinically driven target lesion revascularization (CDTLR) (9.5% vs. 9.5%, P=0.93), and CDTVR (10.7% vs. 10.1%, P=0.80). CDTVR occurred in 41 and 79 patients of the elderly and younger groups, respectively, due to ≥1 of the following reasons: worsening angina (n=30 and 56, respectively), positive FFR measurement (n=23 and 26, respectively), positive non-invasive test (n=12 and 21, respectively), or ischemic changes on electrocardiogram (n=7 and 6, respectively). After multivariable adjustments, elderly patients did not emerge as an independent predictor for TVF and CDTVR (Supplementary Table 1). As an explanatory analysis, we further classified patients into 4 groups according to FFR value (≤0.80, 0.81–0.85, 0.86–0.90, and 0.91–1.00) (Supplementary Tables 2–4) and consistent results were observed across sub-groups. We also assessed the impact of angina symptoms on clinical outcomes in elderly and younger patients (Table 4
and
Supplementary Tables 5,6). There were no significant differences in all-cause and cardiac death between asymptomatic and symptomatic patients in both groups, whereas in the elderly group, symptomatic patients had a higher risk of CDTLR (13.1% vs. 6.2%, P=0.02), CDTVR (14.1% vs. 7.6%, P=0.04), and TVF (17.9% vs. 11.0%, P=0.05) (Table 4). Similar trends were observed after stratifying patients according to FFR values (i.e., FFR ≤0.80 or >0.80) (Table 5).
Table 3.
Clinical Events Over 5 Years
| |
<75 years
(n=829) |
≥75 years
(n=433) |
P value |
| TVF |
86 (10.8) |
55 (14.3) |
0.12 |
| MACE |
116 (14.4) |
114 (28.0) |
<0.001 |
| All-cause death |
37 (4.6) |
80 (19.8) |
<0.001 |
| Cardiac death |
6 (0.8) |
16 (4.4) |
<0.001 |
| Non-cardiac death |
31 (3.9) |
64 (16.1) |
<0.001 |
| TVMI |
7 (0.9) |
4 (1.3) |
0.80 |
| CDTLR |
74 (9.5) |
36 (9.5) |
0.93 |
| CDTVR |
79 (10.1) |
41 (10.7) |
0.80 |
Data are presented as n (%). CDTLR, clinically driven target lesion revascularization; CDTVR, clinically driven target vessel revascularization; MACE, major adverse cardiovascular events; TVF, target vessel failure; TVMI, target vessel-related myocardial infarction.
Table 4.
Clinical Events Over 5 Years According to Age and Symptoms
| |
<75 years |
≥75 years |
Asymptomatic
(n=425) |
Symptomatic
(n=404) |
P value |
Asymptomatic
(n=224) |
Symptomatic
(n=209) |
P value |
| TVF |
45 (11.2) |
41 (10.5) |
0.85 |
22 (11.0) |
33 (17.9) |
0.05 |
| MACE |
62 (15.1) |
54 (13.7) |
0.64 |
54 (25.4) |
60 (30.8) |
0.20 |
| All-cause death |
21 (5.1) |
16 (4.1) |
0.48 |
42 (19.9) |
38 (19.7) |
0.97 |
| Cardiac death |
3 (0.8) |
3 (0.8) |
0.96 |
7 (3.7) |
9 (5.1) |
0.49 |
| Noncardiac death |
18 (4.4) |
13 (3.3) |
0.43 |
35 (16.8) |
29 (15.4) |
0.69 |
| TVMI |
3 (0.7) |
4 (1.0) |
0.66 |
1 (0.6) |
3 (2.0) |
0.27 |
| CDTLR |
38 (9.6) |
36 (9.3) |
0.98 |
12 (6.2) |
24 (13.1) |
0.02 |
| CDTVR |
41 (10.4) |
38 (9.8) |
0.91 |
15 (7.6) |
26 (14.1) |
0.04 |
Data are presented as n (%). Abbreviations as in Table 3.
Table 5.
Clinical Events Over 5 Years According to Age, Symptoms, and FFR Values
| |
<75 years |
≥75 years |
| Asymptomatic |
Symptomatic |
P value |
Asymptomatic |
Symptomatic |
P value |
| FFR ≤0.80 |
(n=83) |
(n=70) |
|
(n=30) |
(n=31) |
|
| TVF |
18 (22.4) |
7 (10.1) |
0.06 |
4 (14.7) |
8 (26.9) |
0.21 |
| MACE |
21 (25.9) |
11 (16.0) |
0.15 |
8 (28.9) |
9 (30.6) |
0.71 |
| All-cause death |
6 (7.5) |
4 (5.9) |
0.68 |
5 (18.4) |
3 (10.5) |
0.45 |
| Cardiac death |
2 (2.5) |
0 (0) |
0.19 |
1 (4.0) |
2 (6.9) |
0.58 |
| Non-cardiac death |
4 (5.1) |
4 (5.9) |
0.84 |
4 (15.0) |
1 (3.8) |
0.16 |
| TVMI |
0 (0) |
1 (1.4) |
0.28 |
0 (0) |
0 (0) |
NA |
| CDTLR |
15 (19.5) |
7 (10.3) |
0.16 |
2 (7.3) |
7 (23.4) |
0.07 |
| CDTVR |
16 (20.6) |
7 (10.3) |
0.12 |
3 (10.7) |
7 (23.4) |
0.18 |
| FFR >0.80 |
(n=342) |
(n=334) |
|
(n=194) |
(n=178) |
|
| TVF |
27 (8.4) |
34 (10.6) |
0.29 |
18 (10.3) |
25 (16.2) |
0.13 |
| MACE |
40 (12.4) |
43 (13.2) |
0.69 |
46 (22.7) |
51 (29.2) |
0.22 |
| All-cause death |
15 (4.6) |
12 (3.7) |
0.59 |
37 (20.1) |
35 (21.3) |
0.81 |
| Cardiac death |
1 (0.3) |
3 (1.0) |
0.31 |
6 (3.7) |
7 (4.7) |
0.62 |
| Non-cardiac death |
14 (4.2) |
9 (2.8) |
0.32 |
31 (17.1) |
28 (17.4) |
0.97 |
| TVMI |
3 (0.9) |
3 (0.9) |
0.98 |
1 (0.7) |
3 (2.4) |
0.25 |
| CDTLR |
23 (7.2) |
29 (9.0) |
0.34 |
10 (6.0) |
17 (11.1) |
0.09 |
| CDTVR |
25 (7.9) |
31 (9.7) |
0.35 |
12 (7.0) |
19 (12.3) |
0.11 |
Data are presented as n (%). NA, not applicable. Other abbreviations as in Table 3.
The %DS values were available in 1,137 patients (1,301 lesions). Patient and lesion characteristics stratified according to age and %DS are summarized in
Supplementary Tables 7
and
8. Among patients with %DS <50%, FFR values in elderly patients were significantly higher than those in younger patients (0.88±0.07 vs. 0.85±0.07, P=0.01), whereas there was no significant difference between groups among patients with %DS ≥50% (0.86±0.06 vs. 0.85±0.06, P=0.23) (Figure 3). In terms of clinical outcomes, cardiac death occurred more frequently in elderly patients than younger patients regardless of %DS, although other outcomes did not differ between groups (Supplementary Table 9
and
Supplementary Figure 1). The distribution of FFR values and %DS according to age is summarized in
Supplementary Figure 2. Compared with younger patients, elderly patients had more lesions with an FFR >0.80 and %DS ≥50% (i.e., mismatch) (25.4% vs. 23.4%) and less lesions with an FFR ≤0.80 and %DS <50% (i.e., reverse mismatch) (8.9% vs. 13.0%) (P=0.09).
Discussion
The present study is the first to explore 5-year outcomes in elderly patients after deferral of revascularization based on FFR, using data from a large-scale, real-world patient cohort. Major findings of the current study are: (1) there was no significant difference in TVF, CDTVR, CDTLR, and TVMI between elderly and younger patients, whereas elderly patients carried an increased risk of mortality; (2) FFR values in lesions with %DS <50% were significantly higher in elderly patients than in younger patients, whereas this relationship was not observed in those with %DS ≥50%; and (3) angina symptoms were associated with a higher risk of revascularization in elderly patients but not in younger patients.
The global demographic shift toward an older population has resulted in a higher burden of CCS patients due to the dominancy of elderly patients among the CCS cohort.15
As elderly patients tend to have atypical symptoms and more complex diseases than younger patients, assessing the functional significance of CAD is highly encouraged to improve their prognosis. Although previous randomized and observational studies have demonstrated the safety of FFR-guided deferral of revascularization for intermediate coronary stenosis,2,4,5
data on long-term outcomes after deferral of coronary revascularization among elderly patients are limited to date. In the current study, an incidence of TVF at 5 years was not significantly different between groups, whereas elderly patients had an increased risk of cardiac and non-cardiac death. Given no difference in CDTVR and TVMI, increased mortality risk is likely due to non-ischemic cardiac causes and comorbidities related to aging. Collectively, our findings confirm that FFR guidance can be safely used for the deferral of revascularization among elderly CCS patients.
The correlation between angiographic DS and FFR is reportedly weak due to several limitations of coronary angiography, especially in mild or intermediate coronary artery stenosis.16
Previous studies comparing FFR values with angiographic DS have reported that advanced age was an independent predictor for the mismatch between angiographic DS and FFR.8,16
A sub-analysis of the FAME (Fractional Flow Reserve versus Angiography for Multivessel Evaluation) study demonstrated that elderly patients had higher FFR values in vessels with 50–70% stenosis (0.83±0.11 vs. 0.80±0.13, P=0.028) and in vessels with 71–90% stenosis (0.69±0.15 vs. 0.65±0.16, P=0.002) compared with younger patients.10
These findings may be attributable to aging-related loss of functional myocytes or attenuation of the vasodilator response to the adenosine.11–13
In the current study, elderly patients with %DS <50% had higher FFR values than younger patients, although the significant difference was not obseved in lesions with %DS ≥50%. Although the results appeared somewhat different from the previous study, it might be due to several differences between studies in terms of the lesion severity (i.e., the previous study did not include lesions with <50%, whereas 70.8% of lesions in the current study showed %DS <50%), %DS evaluation method (visual estimation vs. quantitative coronary angiography), and the definition of elderly patients (≥65 vs. ≥75 years).10
The impact of aging on FFR values, although modest, may be more clinically relevant in patients with a FFR value around the cut-off (i.e., 0.80), which directly affects the decision on subsequent treatment options (i.e., revascularization or medical therapy). However, the current study found no excess risk of ischemic events in elderly patients across sub-groups of FFR categories (i.e., ≤0.80, 0.81–0.85, 0.86–0.90, 0.91–1.00), suggesting that borderline FFR can also be safely used as a decision-making tool among elderly patients.
In the current study, elderly patients with angina symptoms had a higher risk of revascularization than those without symptoms, whereas this difference was not observed in younger patients. Similarly, a previous sub-analysis of the J-CONFIRM registry reported that symptomatic patients had significantly higher rates of TVF (6.2% vs. 3.3%; P=0.01) and CDTVR (6.2% vs. 3.1%; P=0.009) at 2 years than asymptomatic patients despite the lack of functional significance of CAD (i.e., FFR >0.80).17
These findings might be partly explained by microvascular angina, which is one of the underlying mechanisms of angina symptoms in patients with non-functionally significant CAD18
and is more dominant in elderly patients than in younger patients.19
As the current study did not assess microvascular function, further studies are warranted to evaluate whether microvascular dysfunction would affect clinical outcomes after FFR-based deferral of revascularization in elderly patients. Nevertheless, our results suggested that clinical symptoms deserve attention even after the FFR-guided deferral of revascularization, especially in elderly patients.
Study Limitations
Several limitations apply to the presnt study. First, the lack of significant differences between groups may be partly attributable to the lack of power due to a relatively small sample size and the low incidence of ischemic events, despite a large-scale dataset with a 5-year follow-up. Second, lifestyle modification and the control of risk factors plays crucial roles in the management of CCS patients; however, we could not determine whether they were optimally achieved during the follow-up period. Third, several potential confounding factors that may affect FFR values, including microcirculatory dysfunction, left ventricular hypertrophy, and dominancy of coronary artery, were not considered in the current analysis. These might have affected the conclusions in the present study. Finally, extrapolation of our results outside Japan requires caution because this study population consisted solely of Japanese people.
Conclusions
Elderly patients had no excess risk of ischemic events related to the deferred coronary lesions by FFR, although FFR values in mild coronary artery stenoses were somewhat different between elderly and younger patients.
Acknowledgments
The authors appreciate the efforts of the investigators in the 28 participating centers.
Sources of Funding
This work was supported by Abbott Medical Japan, Phillips Japan, and Boston Scientific Japan.
Disclosures
S.K. receives lecture fees from Abbott Medical Japan and Boston Scientific Japan; H.M. receives lecture fees from Abbott Medical Japan, Phillips Japan, and Boston Scientific Japan; Y.K. receives lecture fees from Abbott Medical Japan and Phillips Japan; T.A. receives lecture fees from Abbott Medical Japan and Phillips Japan; K.T. is a member of
Circulation Journal’s Editorial Team; H.Y. receives lecture fees from Boston Scientific Japan; N.T. serves as advisory board member for Abbott Medical Japan and Boston Scientific Japan. The other authors have no financial disclosures to declare.
IRB Information
This study was approved by the institutional review board of Kokura Memorial Hospital (reference number 18041151).
Data Availability
The deidentified participant data will not be shared.
Supplementary Files
Please find supplementary file(s);
http://dx.doi.org/10.1253/circj.CJ-21-1024
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