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Rates of future hemodialysis risk and beneficial outcomes for patients with chronic kidney disease undergoing recanalization of chronic total occlusion
International Journal of Cardiology 222 (2016) 707–713
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International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Rates of future hemodialysis risk and beneficial outcomes for patients with chronic kidney disease undergoing recanalization of chronic total occlusion Tetsuro Shimura MD a, Masanori Yamamoto MD a,⁎, Etsuo Tsuchikane MD a,⁎, Tomohiko Teramoto MD a, Masashi Kimura MD a, Hitoshi Matsuo MD b, Yoshiaki Kawase MD b, Yoriyasu Suzuki MD c, Seiji Kano MD c, Maoto Habara MD a, Kenya Nasu MD a, Yoshihisa Kinoshita MD a, Mitsuyasu Terashima MD a, Tetsuo Matsubara MD a, Takahiko Suzuki MD a a b c
Department of Cardiovascular Medicine, Toyohashi Heart Center, Toyohashi, Aichi, Japan Department of Cardiovascular Medicine, Gifu Heart Center, Gifu, Japan Department of Cardiovascular Medicine, Nagoya Heart Center, Nagoya, Aichi, Japan
a r t i c l e
i n f o
Article history: Received 6 May 2016 Received in revised form 1 August 2016 Accepted 2 August 2016 Available online 04 August 2016 Keywords: Coronary artery disease Chronic kidney disease Chronic total occlusion Percutaneous coronary intervention Hemodialysis
a b s t r a c t Background: This study aimed to assess the prognosis and deleterious effects of chronic kidney disease (CKD) on future renal function, in patients who had undergone chronic total occlusion-percutaneous coronary intervention (CTO-PCI). Methods: The treatment effects were studied in 739 patients who underwent CTO-PCI. The patients were divided into 3 groups according to estimated glomerular filtration rate (eGFR): non-CKD (eGFR ≥ 60 ml/min/1.73m2, n = 562), CKD-1 (45 ≤ eGFR b 60 ml/min/1.73m2, n = 90), and CKD-2 (eGFR b 45 ml/min/1.73m2, n = 87). Future hemodialysis (HD) rates and the prevalence of acute kidney injury (AKI) except for 45 patients undergoing regular HD, and other clinical and prognostic outcomes were compared between the 3 groups. Results: Procedural success rates showed trends toward lower prevalence across the 3 groups (89.5%, 84.4%, and 81.6%, p = 0.060). The prevalence of AKI significantly differed between the 3 groups (4.6%, 8.9%, and 16.7%, p = 0.001), whereas no patients were introduced to regular HD at discharge. During a median follow-up period of 51.2 ± 28.9 months, newly required HD significantly differed between the 3 groups (0.7%, 0%, and 7.1%, p b 0.001). When compared with unsuccessful CTO-PCI, successful CTO-PCI was found to improve cardiovascular mortality in the non-CKD and CKD-1 (Log-rank test: p = 0.025, p = 0.024, respectively) and to improve both cardiovascular and all-cause mortality in the CKD-2 (Log-rank test: p = 0.027, p = 0.0022, respectively). Conclusions: Although CTO-PCI for patients with advanced CKD was associated with a high risk of future HD introduction, not directly owing to CTO-PCI and AKI, successful treatment of CTO might contribute to better survival benefit regardless of the presence or absence of CKD. © 2016 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Recanalization of chronic total occlusion (CTO) by percutaneous coronary intervention (PCI) still remains a challenge in terms of technique and uncertainty of clinical advantages. The beneficial effects of this treatment is difficult to evaluate objectively, whereas studies evaluating the effects of CTO-PCI on prognosis, have reported that prognosis im⁎ Corresponding authors at: Department of Cardiovascular Medicine, Toyohashi Heart Center, 21-1, Gobudori, Ohyama-cho, Toyohashi, Aichi 441-8530, Japan. E-mail addresses: [email protected] (M. Yamamoto), [email protected] (E. Tsuchikane).
http://dx.doi.org/10.1016/j.ijcard.2016.08.019 0167-5273/© 2016 Elsevier Ireland Ltd. All rights reserved.
proved indirectly or consistently in the successful CTO treatment group as compared to the failure of CTO treatment group [1–5]. Patient backgrounds and lesion characteristics are important factors for the successful treatment of CTO. Patients with renal dysfunction are especially likely to be found in the failure group because of its lesion complexity. Patients with chronic kidney disease (CKD) who were undergoing invasive treatments were generally associated with poorer prognosis than patients without CKD [4–8]. Therefore, presence or absence of CKD, and the severity of disease may have an influence on prognosis, regardless of success or failure of CTO-PCI. CKD is a general term for heterogeneous disorders affecting kidney function. Few studies have investigated the clinical outcomes between CKD grading and CTO-PCI.
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Patients with CKD may have less benefits depending on their CKD severity, even though CTO-PCI was successfully performed. In addition, little is known regarding the clinical concerns of introduction of regular hemodialysis (HD) at acute and late phase in these cohorts. Therefore, we retrospectively studied the deleterious effects of CKD and its severity on clinical outcomes including serial renal function change in patients who underwent CTO-PCI. 2. Methods 2.1. Patient population Consecutive patients who underwent CTO-PCI were extracted from the database of the Toyohashi Heart Center, Toyohashi, Japan, in which data were entered prospectively. In this retrospective study, pretreatment and posttreatment clinical data were collected from a single-center PCI registry. The database included relevant patient information and angiographic and procedural characteristics. For this study 7353 PCI procedures performed between January 2006 and December 2013 were screened, of which 848 involved revascularization of a CTO. Patients who underwent CTOs in more than one vessel or lesions in a small coronary branch vessel, and those in whom a repeat procedure succeeded an initial failure were excluded from the study, as were the few patients who were untraceable. We excluded patients with CTO lesions in more than one vessel in order to evaluate the effect of a single CTO-PCI recanalization and those with small-branch lesions because of the known lesser clinical advantage in such cases. The remaining 739 patients represented the total study population. The patients include, who underwent CTO-PCI were divided into 3 groups according to estimated glomerular filtration rate (eGFR). Patients with eGFR ≥60 ml/min/1.73 m2 were classified in the non-CKD group; those with 45 ml/min/1.73 m2 ≤ eGFR b60 ml/min/1.73 m2 in the CKD-1 group; and those with eGFR b45 ml/min/1.73 m2, in the CKD-2 group. eGFR was calculated according to the CKD guidelines proposed by the Japanese Society of Nephrology on the based on the modified Modification of Diet in Renal Disease equation [9]. 2.2. Definitions Coronary CTO was defined as a true total occlusion with complete interruption of antegrade blood flow as assessed by using coronary arteriography (thrombolysis in myocardial infarction [TIMI] flow grade 0) and with estimated occlusion duration of 3 months or longer. For the procedural background inherent in this study, we examined the total amount of contrast medium, procedure time, and radiation dose. Procedure time was defined as the total duration of the patient's stay in the catheterization room (from entry until exit). Fluoroscopy time and radiation dose were recorded automatically by the cine device. Coronary perforation was examined as a possible complication of the procedure. These information were corrected from our single-center PCI registry database as we previously reported [10]. The registry data included the total amount of contrast media, procedure time, and radiation dose during all CTO procedures. The following endpoints were evaluated to compare patients in whom the procedure failed and those in whom the procedure was successful: all-cause death and evident cardiac death. Evident cardiac death was defined as heart failure, myocardial infarction (MI), or unexpected death presumed to be due to ischemic cardiovascular disease and arrhythmia that occurred within 24 h after the onset of symptoms, without clinical or postmortem evidence of another cause,
and this was judged according to the information from the telephonic interview with the patient and patient's family. Death from uncertain causes was also classified as cardiac death. Double CTO was defined as the presence of a CTO lesion in more than one vessel at the same time. Procedural success was defined as residual stenosis of ≤50% with TIMI flow grade 3 and without major adverse cardiovascular events. Periprocedural MI was diagnosed based on an increase in creatinine kinase level to twice the upper limit of normal. The definition of acute kidney injury (AKI) was modified by using the Kidney Disease Improving Global Outcomes Guidelines definition as follows: ≥0.3 mg/dl at discharge after the procedure or ≥50% increase in serum creatinine level from its baseline value to its post–cardiac catheterization peak level at any time during hospitalization [11]. Baseline creatinine level was defined as the most recent serum creatinine level measured prior to the procedure. Acute Kidney Injury Network stage 2 (AKIN2) was defined as a doubling in the baseline serum creatinine level or the development of a new dialysis-dependent renal failure [12].
2.3. Data acquisition Clinical data from all the patients with CTO lesions treated invasively were prospectively recorded in a computerized database as a single-center PCI registry [10]. The recorded data included patient status, clinical characteristics, laboratory data, presence of concomitant diseases, characteristics of CTO lesions, angiographic findings, revascularization procedure, and in-hospital mortality. Whether HD was required during the follow-up period was also evaluated based on individual patient charts. The mean follow-up period was 51.2 ± 28.9 months. These strategies made it possible to collect data.
2.4. Invasive treatment and medications All the patients were treated with elective PCI because of stable angina or asymptomatic myocardial ischemia. The patients received aspirin (100 mg) and ticlopidine (200 mg) or clopidogrel (75 mg) daily before the intervention. Other medications were continued during hospitalization. Patients with CKD-2 and CKD-3 group received hydration to prevent the occurrence of AKI before the CTO procedure. The hydration regimens were administered according to previous recommendations: isotonic sodium chloride solution or lactate ringer solution were started with an infusion rate of 1 ml/kg of body weight per hour 12 h before and (continued 12 h) after procedure. However, the hydration volume control varied in each patient due to the presence of multiple co-morbidities such as age, renal function and ejection fraction.
2.5. Statistical analyses The primary outcome of this study was all-cause mortality after PCI. Results are presented as mean, SD, or numbers and percentages. The study groups were compared by using one-way analysis of variance for continuous variables and χ2 test. Long-term outcomes were presented by using Kaplan-Meier survival curves and compared by using the log-rank test. Data with p values b 0.05 were considered statistically significant. Univariate logistic regression analysis was performed to evaluate the associations between the clinical parameters and AKI. Thereafter, multivariate analysis was performed the factors in univariate analysis with p-value b 0.05 to assess their independent association of AKI after procedure.
Table 1 Baseline patient characteristics in CKD group allocation. Baseline patient characteristics in CKD group allocation
Non-CKD (eGFR ≧ 60) n = 562
CKD-1 group (45 ≦ eGFR b 60) n = 90
CKD-2 group (eGFR b 45) n = 87
P value
Age, yrs ≧80 yrs Male Diabetes mellitus Hypertension Hyperlipidemia Prior CABG Prior PCI Prior CI Smoking Family history Body weight, kg Body height, m Body mass index (BMI) Laboratory data Creatinine (mg/dL) Blood urea nitrogen (mg/dL) eGFR (ml/min/1.73m2) Patient with hemodialysis
64.6 ± 10.7 40 (7.1%) 485 (86.3%) 60 (10.7%) 329 (58.5%) 241 (42.9%) 56 (10.0%) 17 (3.0%) 160 (28.5%) 154 (27.4%) 89 (15.8%) 65.3 ± 12.6 163.1 ± 8.0 24.4 ± 3.7
71.4 ± 9.1 18 (20.0%) 67 (74.4%) 10 (11.1%) 51 (56.7%) 33 (36.7%) 12 (13.3%) 0 (0%) 28 (31.1%) 14 (15.6%) 10 (11.1%) 62.5 ± 10.5 160.6 ± 8.2 24.1 ± 3.0
68.6 ± 10.6 19 (21.8%) 64 (73.6%) 17 (19.5%) 58 (66.7%) 20 (23.0%) 8 (9.2%) 3 (3.4%) 33 (37.9%) 8 (9.2%) 7 (8.0%) 60.7 ± 12.4 161.3 ± 8.9 23.1 ± 3.8
b0.001 b0.001 0.001 0.057 0.31 0.002 0.58 0.23 0.19 b0.001 0.101 0.001 0.09 0.012
0.83 ± 0.15 15.4 ± 4.0 83.4 ± 16.9 0 (0%)
1.13 ± 0.14 19.9 ± 5.5 54.0 ± 4.0 0 (0%)
5.49 ± 3.8 37.4 ± 14.6 19.7 ± 16.7 45 (51.7%)
b0.001 b0.001 b0.001 b0.001
Values are n (%) or mean ± SD. CABG, Coronary artery bypass grafting; PCI, Percutaneous coronary intervention; CI, Cerebral infarction; eGFR, estimated glomerular filtration rate.
T. Shimura et al. / International Journal of Cardiology 222 (2016) 707–713
3. Results 3.1. Baseline and procedural characteristics The baseline patient characteristics significantly differed between the 3 groups (Table 1). Approximately half of the patients in CKD-2 group (45/87, 51.7%) were undergoing regular HD before receiving CTO-PCI. Patient age, sex, and body characteristics, including weight and body mass index, showed significant differences between the 3 groups. The baseline lesion and procedural characteristics are presented in Table 2. The prevalence rates of severe calcified lesion, use of a rotablator for recanalization, and use of intra-aortic balloon pumping were significantly higher across the 3 groups (p b 0.001, p b 0.001, and p b 0.001, respectively). These results were considered to reflect the lesion and procedural complexity in advanced-stage CKD. As a result, procedural success rates showed trends toward lower prevalence rates across the 3 groups (89.5% vs. 84.4% vs. 81.6%, p = 0.060). The operators reduced the use of contrast medium in the patient groups with higher renal impairment (303.6 ± 153.3 ml vs. 268.9 ± 161.4 ml vs.
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211.9 ± 120.8 ml, p b 0.001). Procedural time and complications such as dissection and coronary perforation did not differ between the 3 groups. In the CKD-2 group, 45 patients were excluded from the analysis concerning the prevalence of AKI and new hemodialysis introduction after CTO-PCI. The prevalence of AKI stage 1 was significantly higher in the CKD-2 group than in the other two groups (26/562 [4.6%] vs. 8/ 90 [8.9%] vs. 7/42 [16.7%], p = 0.001]. AKI stage 2 occurred only in one patient in the CKD-1 group (0/562 [0%] vs. 1/90 [1.1%] vs. 0/42 [0%], p = 0.001), and none of the patients had AKI stage 3. Logistic regression analysis for the relationship between the clinical factors and AKI are shown in Table 3. Presence of CKD and contrast volume were independent predictors of the increasing risk of AKI (OR = 2.40, 95% confidence interval [CI] = 1.53–3.76, p b 0.001; and OR = 1.002, 95% CI = 1.00– 1.004, p = 0.022; respectively). None of the patients in CKD-2 group was introduced to regular HD at discharge. Moreover, none of the patients enrolled in this study were introduced to regular HD at discharge. Two patients with AKI stage 1 were finally introduced to regular HD during the follow-up period. However, the patient with AKI stage 2 did not need regular HD during the follow-
Table 2 Baseline lesion and procedural characteristics. Baseline lesion and procedural characteristics Location of CTO RCA LAD LCx LMT Lesion characteristics In stent occlusion Ulceration Irregularity Eccentricity Bifurcation at CTO site Calcification None, Mild Moderate Severe Tortuosity None, Mild Moderate Severe Legion Length b10 mm 10 mm ≦ b 20 mm 20 mm ≦ Use of Rotablator Use of IABP Success rate Dilatation strategies (success case only) Non stent use BMS use DES use Complications Coronary dissection No coronary dissection Dissection with flow limitation Dissection without flow limitation Coronary perforation No coronary perforation Perforation type 1 Perforation type 2 Procedure time (min) Contrast volume (ml) Acute Kidney Injury AKI stage 1 AKI stage 2 AKI stage 3 Newly required hemodialysis At discharge At follow-up period
Non-CKD (eGFR ≧ 60) n = 562
CKD-1 group (45 ≦ eGFR b 60) n = 90
CKD-2 group (eGFR b 45) n = 87
281 (50.0%) 168 (29.9%) 112 (19.9%) 1 (0.2%)
34 (37.8%) 30 (33.3%) 23 (25.6%) 3 (3.3%)
43 (49.4%) 21 (24.1%) 23 (26.4%) 0 (0%)
61 (10.9%) 4 (0.7%) 10 (1.8%) 256 (45.6%) 107 (19.0%)
12 (13.3%) 1 (1.1%) 2 (2.2%) 34 (37.8%) 23 (25.6%)
14 (16.1%) 0 (0%) 3 (3.4%) 40 (46.0%) 13 (14.9%)
0.33 0.65 0.58 0.37 0.19
377 (67.1%) 135 (24.0%) 50 (8.9%)
55 (61.1%) 28 (31.1%) 7 (7.8%)
32 (36.8%) 29 (33.3%) 26 (29.9%)
b0.001
432 (76.9%) 97 (17.3%) 33 (5.9%)
69 (76.7%) 14 (15.6%) 7 (7.8%)
64 (73.6%) 16 (18.4%) 7 (8.0%)
0.88
3 (0.5%) 94 (16.7%) 465 (82.7%) 38 (6.8%) 11 (2.0%) 503 (89.5%)
3 (3.3%) 12 (13.3%) 75 (83.3%) 3 (3.3%) 6 (6.7%) 76 (84.4%)
3 (3.4%) 17 (19.5%) 67 (77.0%) 18 (20.7%) 10 (11.5%) 71 (81.6%)
0/503 (0%) 17/503 (3.4%) 486/503 (96.6%)
0/76 (0%) 4/76 (5.3%) 72/76 (94.7%)
0/71 (0%) 2/71 (2.8%) 69/71 (97.2%)
0.67
512 (91.1%) 2 (0.4%) 48 (8.5%)
82 (91.1%) 1 (1.1%) 7 (7.8%)
77 (88.5%) 0 (0%) 10 (11.5%)
0.66
497 (88.4%) 62 (11.0%) 3 (0.5%) 189.4 ± 90.2 303.6 ± 153.3
77 (85.6%) 12 (13.3%) 1 (1.1%) 197.3 ± 92.0 268.9 ± 161.4
79 (90.8%) 8 (9.2%) 0 (0%) 188.1 ± 87.0 211.9 ± 120.8
0.72 b0.001
26 (4.6%) 0 (0%) 0 (0%)
8 (8.9%) 1 (1.1%) 0 (0%)
7/42 (16.7%) 0/42 (0%) 0/42 (0%)
0.001 0.001 N0.99
0 (0%) 4 (0.7%)
0 (0%) 0 (0%)
0/42 (0%) 3/42 (7.1%)
N0.99 b0.001
P value
0.002
0.035 b0.001 b0.001 0.060
0.77
Values are n (%) or mean ± SD. CTO, Chronic total occlusion; RCA, Right coronary artery; LAD, Left anterior descending coronary artery; LCx, Left circumflex coronary artery; LMT, Left main trunk coronary artery; IABP, Intra-aortic balloon pumping; BMS, Bare metal stent; DES, Drug eluting stent; AKI, acute kidney injury.
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Table 3 Odds ratio analysis for the association between patient/lesion characteristics and acute kidney injury. Univariate analysis Adjusting factors Baseline clinical characteristics Age (per 1 year increase) Male (for female) Body mass index (per 1 m2 increase) Diabetes mellitus Hypertension Hyperlipidemia Chronic kidney disease (per 1 group increase) Baseline lesion and procedural characteristics In stent occlusion (for no in stent occlusion) Ulceration (for no ulceration) Irregularity (for no irregularity) Eccentricity (for no eccentricity) Bifurcation at CTO site Calcification (per 1 category increase) Tortuosity (per 1 category increase) Legion Length (per 1 category increase) Post procedural variables Procedure success (for failure) Procedure time (min) Contrast volume (ml)
Multivariate analysis
Odds ratio
95% confidence interval
p value
Odds ratio
95% confidence interval
p value
1.04 0.49 1.02 1.75 1.59 0.99 2.08
1.004–1.07 0.54–3.66 0.94–1.11 0.75–4.09 0.81–3.11 0.52–1.86 1.36–3.16
0.093 0.49 0.62 0.20 0.18 0.97 0.001
2.23
1.40–3.55
b0.001
0.81 0.00 1.42 0.77 1.95 1.44 1.36 1.09
0.28–2.33 0.00 0.18–11.3 0.41–1.47 0.98–3.86 0.94–2.21 0.85–2.20 0.59–2.40
0.70 0.99 0.74 0.43 0.056 0.097 0.20 0.83
0.51 1.004 1.002
0.23–1.15 1.001–1.007 1.001–1.004
0.10 0.008 0.007
1.002 1.002
1.00–1.006 1.00–1.004
0.29 0.022
CTO, Chronic total occlusion.
up period. The prevalence of newly required HD during the follow-up period significantly differed between the 3 groups (4/562 [0.7%] vs. 0/ 91 [0%] vs. 3/43 [7.0%], respectively; p b 0.001). 3.2. Long-term mortality During a median follow-up of 51.2 ± 28.9 months after discharge, 85 of the 739 patients died during the follow-up period. Of these, 56 patients died from a cardiovascular event. Details on the clinical outcomes of the 7 patients who were newly introduced to HD are presented in Table 4. Although 4 of the 7 patients died during the follow-up period, the causes of their deaths were thought to be associated with multiple factors beyond renal failure itself. Of the 4 patients, none died immediately after the introduction of HD. Only 2 of the 7 patients developed AKI stage 1 after the CTO procedure. One of them was in the CKD-2 group and introduced to regular HD 828 days after CTO-PCI. Another patient who belonged to the non-CKD group was introduced to regular HD 72 days after the PCI procedure. To begin with, the time from the PCI procedure to regular HD introduction differed greatly between the 7 patients (range, 72–2299 days). The cumulative mortality rates in each of the 3 CKD stages were compared for the 2 different groups between CTO-PCI success and failure by using Kaplan-Meier curves. The all-
cause mortality in the non-CKD group showed no significant difference between the success and failure groups (log-rank test: p = 0.45). Meanwhile, the cardiovascular mortality in the success group was significantly lower than that in the failure group (p = 0.025; Fig. 1-A, B). Similar results regarding all-cause mortality (p = 0.23) and cardiovascular mortality (p = 0.024) were found in the CKD-1 group between the success and failure groups (Fig. 2-A, B). By contrast, the patients in the CKD2 group who had a successful PCI were associated with better clinical outcomes in terms of both all-cause and cardiovascular mortality than those who had a failed PCI (p = 0.027 and p = 0.0022, respectively; Fig. 3-A, B). 4. Discussion The results of the present study demonstrated two major findings. First, successful CTO-PCI, when compared with failed CTO-PCI, significantly improved the cardiovascular mortality of the patients in the non-CKD and CKD-1 groups (45 ml/min/1.73 m2 ≤ eGFR b60 ml/min/ 1.73 m2). Furthermore, it improved the all-cause and cardiovascular mortality of the patients in the advanced CKD-2 group (eGFR b45 ml/min/1.73 m2). Previous research proved that the prognosis in the successful CTO treatment group was better than that in the failed
Table 4 Patient characteristics of newly required hemodialysis after CTO-PCI. Patient age Gender
eGFR
Creatinine (baseline)
Creatinine (discharge)
Procedure time
Contrast volume
AKI
Procedure success
Time from procedure to HD
Follow-up period
Outcomes Cause of death
53 years Male 79 years Male 64 years Male 75 years Female 73 years Male 68 years Male 70 years Male
136.7 ml/min/1.73m2
0.56 mg/dl
0.60 mg/dl
195 min
320 ml
(−)
(+)
2299 days
2299 days
Alive
76.8 ml/min/1.73m2
0.86 mg/dl
1.50 mg/dl
265 min
374 ml
Stage1
(+)
72 days
213 days
69.8 ml/min/1.73m
2
0.97 mg/dl
0.94 mg/dl
220 min
180 ml
(−)
(+)
856 days
1133 days
67.2 ml/min/1.73m
2
0.75 mg/dl
1.00 mg/dl
340 min
350 ml
(−)
(+)
1768 days
2612 days
Death heart failure Death septic shock Alive
37.1 ml/min/1.73m2
1.64 mg/dl
1.96 mg/dl
122 min
65 ml
Stage 1
(+)
828 days
1042 days
32.5 ml/min/1.73m2
1.86 mg/dl
1.99 mg/dl
189 min
400 ml
(−)
(+)
1640 days
1956 days
2
4.09 mg/dl
2.82 mg/dl
175 min
120 ml
(−)
(+)
102 days
1658 days
13.0 ml/min/1.73m
eGFR, estimated glomerular filtration rate; HD, hemodialysis; AKI, acute kidney injury.
Death heart failure Alive Death critical limb ischemia
T. Shimura et al. / International Journal of Cardiology 222 (2016) 707–713
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Fig. 1. A Kaplan-Meier curve showing differences in all-cause mortality between successful and failed CTO-PCI in the non-CKD group. There were no statistical differences between successful and failed CTO-PCI in The non-CKD group patients. B Kaplan-Meier curve showing differences in cardiovascular mortality between successful and failed CTO-PCI in the nonCKD group. Successful CTO-PCI in the non-CKD group patients was associated with a decrease in cardiovascular mortality compared to the failed CTO-PCI group.
CTO treatment group [1–5]. In addition, CKD was associated with increased mortality after CTO-PCI [4,5]. It remains uncertain whether patients with an advanced CKD stage would receive the clinical benefits of CTO-PCI depending on the severity of their CKD, even though CTO-PCI is successfully performed. Invasive CTO-PCI for patients with advanced CKD stage is generally considered challenging. In fact, a trend toward low success rates of CTO-PCI was found in the advanced CKD group with severe calcified lesions. However, the beneficial outcomes of successful CTO-PCI as compared with an unsuccessful procedure were not attenuated after the subdivision of the CKD stages. This was especially emphasized in the patients with severely reduced kidney function (eGFR b 45 ml/min/1.73 m2). Recent large-scale data revealed a steep increase in the risk for cardiovascular mortality in advanced CKD groups and underlined the importance of the subdivision of CKD groups by using a threshold eGFR of 45 ml/min/1.73 m2 for each CKD stage [13, 14]. The present results also revealed that the cumulative mortality rates in the CKD-2 group regardless of success or failure of the CTOPCI were higher than those in the non-CKD and CKD-1 groups. If CTOPCI were to be performed in such patients with advanced CKD, operators should understand the poor prognosis in this cohort and continue efforts to improve their technical skills in the recanalization of the artery with CTO.
Second, this study provides data on the prevalence rates of newly required HD in a CTO-PCI cohort. Excessive procedure time and amount of contrast medium were needed during the complex CTO-PCI in some cases. The physicians therefore hesitated in performing CTO-PCI for these patients with advanced CKD when they were concerned about the increased risk of procedure-related kidney injury. Our study also revealed advanced CKD class and contrast volume were independent risk factors of AKI as previous investigations demonstrated [8,10]. The operators tried to reduce the volume of contrast media in the advanced CKD groups, the mean dose of contrast medium used was 200 ml more than that used in conventional PCI [15]. Nevertheless, in such a negative situation, only 42 patients (5.7%) developed AKI; and none of them was introduced to regular HD until the discharge period. Moreover, only 2 patients developed AKI and were finally introduced to regular HD during the follow-up period. One of them belonged to the non-CKD group. He had blue toe syndrome after percutaneous peripheral intervention 2 months after the CTO procedure. His serum creatinine level increased from 0.97 mg/dL to 4.15 mg/dL after the procedure, which led to the introduction of regular HD. The other patient was from the CKD-2 group and was introduced to regular HD 828 days after the CTO procedure because of the natural history of CKD. These results may suggest that the occurrence of AKI does not directly relate to an
Fig. 2. A Kaplan-Meier curve showing differences in all-cause mortality between successful and failed CTO-PCI in the non-CKD group. There were no statistical differences between successful and failed CTO-PCI in the CKD-1 group patients. B Kaplan-Meier curve showing differences in cardiovascular mortality between successful and failed CTO-PCI in the nonCKD group. Successful CTO-PCI in the CKD-1 group patients was associated with a decrease in cardiovascular mortality compared to the failed CTO-PCI group.
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Fig. 3. A Kaplan-Meier curve showing differences in all-cause mortality between successful and failed CTO-PCI in the non-CKD group. Successful CTO-PCI in CKD-2 group patients was associated with a decrease in all-cause mortality compared to failed CTO-PCI group. B Kaplan-Meier curve showing differences in cardiovascular mortality between successful and failed CTO-PCI in the non-CKD group. Successful CTO-PCI in the CKD-2 group patients was associated with a decrease in cardiovascular mortality compared to the failed CTO-PCI group.
early- and late-phase HD introduction. The actual prevalence rates of late-phase HD introduction in the 3 groups were 0.7%, 0%, and 7%, respectively. The higher prevalence of future HD introduction in the patients with eGFR of b45 ml/min/1.73 m2 should be highlighted, whereas these results were quite comparable with those of other conventional invasive procedures [16]. In addition, time from procedure to HD introduction widely ranged from 72 to 2299 days, depending on the background differences between the 7 patients, as partially mentioned earlier. Of these patients, 4 died, although not immediately after HD introduction. The interval between new HD introduction and date of death was quite long (minimum, 213 days). The causes of death, such as heart failure, septic shock, or critical limb ischemia, were not considered to be directly due to renal failure itself. The above-mentioned findings might be informative for decision making in CTO-PCI for patients with advanced CKD, when taking into account the risk-benefit balance.
However, the risk of AKI and future HD introduction in the advanced CKD group was notable, although none of the patients was introduced to maintenance HD immediately after the procedure. Therefore, successful treatment of CTO might contribute to better survival benefit regardless of the presence or absence of CKD. Funding sources None. Disclosures None. Conflict of interest statement There are no conflicts of interest to declare.
4.1. Study limitations References This study has several limitations. First, the success of CTO-PCI is highly dependent on the physician's technique and experience. Although our hospital's experience in performing CTO-PCI has accumulated, the results in acute successful cases may differ under conditions with less physician experience. Second, as this is a retrospective observational study, it has inherent limitations. Third, 45 of the 87 patients in the CKD-2 group were already undergoing maintenance HD. No statistical differences in clinical outcomes were found between the patients with HD in the CKD-2 group (n = 45) and those in the non-HD group (n = 42) in this study. A sample volume of 40 patients divided into success and failure groups was not enough to provide the additional information. A large number of patients would be required to prove the clinical outcomes of CTO-PCI under classified CKD staging. Therefore, we cannot overstate our study conclusions. Finally, the majority of enrolled patients in our study are Japanese. Recent report revealed that cardiovascular disease risk differed in subjects with CKD by races [17]. When considered the race differences, the current results might not be similar. 5. Conclusions Successful CTO-PCI, compared with failed CTO-PCI, significantly improved the cardiovascular mortality of the patients in the non-CKD and mild CKD groups. Furthermore, it improved the all-cause and cardiovascular mortality of the patients in the advanced CKD group.
[1] J.A. Suero, S.P. Marso, P.G. Jones, et al., Procedural outcomes and long-term survival among patients undergoing percutaneous coronary intervention of a chronic total occlusion in native coronary arteries : a 20-year experience, J. Am. Coll. Cardiol. 38 (2001) 409–414. [2] R. Mehran, B.E. Claessen, C. Godino, et al., Multinational chronic total occlusion registry. Long-term outcome of percutaneous coronary intervention for chronic total occlusions, JACC Cardiovasc. Interv. 4 (2011) 952–961. [3] E.L. Hannan, C. Wu, G. Walford, et al., Incomplete revascularization in the era of drug-eluting stents: impact on adverse outcomes, JACC Cardiovasc. Interv. 2 (2009) 17–25. [4] S. George, J. Cockburn, T.C. Clayton, et al., Long-term follow-up of elective chronic total coronary occlusion angioplasty, J. Am. Coll. Cardiol. 64 (2014) 235–243. [5] D.A. Jones, R. Weerackody, K. Rathod, et al., Successful ecanalization of chronic total occlusion in associated with improved long-term survival, J. Am. Coll. Cardiol. Intv. 5 (2012) 380–388. [6] S.S. Naidu, F. Selzer, A. Jacobs, et al., Renal insufficiency is an independent predictor of mortality after percutaneous coronary intervention, Am. J. Cardiol. 92 (2003) 1160–1164. [7] V. Chan, E. Jamieson, A.G. Fleisher, D. Denmark, F. Chan, E. Germann, Valve replacement surgery in end-stage renal failure: mechanical prostheses versus bioprostheses, Ann. Thorac. Surg. 81 (2006) 857–862. [8] M. Yamamoto, K. Hayashida, G. Mouillet, et al., Prognostic value of chronic kidney disease after transcatheter aortic valve implantation, J. Am. Coll. Cardiol. 62 (2013) 869–877. [9] S. Matsuo, E. Imai, M. Horio, et al., Collaborators developing the Japanese equation for estimated GFR. Revised equations for estimated GFR from serum creatinine in Japan, Am. J. Kidney Dis. 53 (2009) 982–992. [10] T. Teramoto, E. Tsuchikane, H. Matsuo, et al., Initial success rate of percutaneous coronary intervention for chronic total occlusion in a native coronary artery is decreased in patients who underwent previous coronary artery bypass graft surgery, J. Am. Coll. Cardiol. Intv. 7 (2014) 39–46.
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mortality. A collaborative meta-analysis of high-risk population cohorts, Kidney Int. 79 (2011) 1341–1352. [15] Y.H. Liu, Y. Liu, N. Tan, et al., Contrast-induced nephropathy following chronic total occlusion percutaneous coronary intervention in patients with chronic kidney disease, Eur. Radiol. 25 (2015) 2274–2281. [16] G. Ashrith, M.A. Elayda, J.M. Wilson, Revascularization options in patients with chronic kidney disease, Tex. Heart Inst. J. 37 (2010) 9–18. [17] L. Liu, Using multivariate quantile regression analysis to explore cardiovascular risk differences in subjects with chronic kidney disease by race and ethnicity: findings from the US chronic renal insufficiency cohort study, Int. Cardiovasc. Forum J. 2 (2015) 20–26.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Rates of future hemodialysis risk and beneficial outcomes for patients with chronic kidney disease undergoing recanalization of chronic total occlusion Tetsuro Shimura MD a, Masanori Yamamoto MD a,⁎, Etsuo Tsuchikane MD a,⁎, Tomohiko Teramoto MD a, Masashi Kimura MD a, Hitoshi Matsuo MD b, Yoshiaki Kawase MD b, Yoriyasu Suzuki MD c, Seiji Kano MD c, Maoto Habara MD a, Kenya Nasu MD a, Yoshihisa Kinoshita MD a, Mitsuyasu Terashima MD a, Tetsuo Matsubara MD a, Takahiko Suzuki MD a a b c
Department of Cardiovascular Medicine, Toyohashi Heart Center, Toyohashi, Aichi, Japan Department of Cardiovascular Medicine, Gifu Heart Center, Gifu, Japan Department of Cardiovascular Medicine, Nagoya Heart Center, Nagoya, Aichi, Japan
a r t i c l e
i n f o
Article history: Received 6 May 2016 Received in revised form 1 August 2016 Accepted 2 August 2016 Available online 04 August 2016 Keywords: Coronary artery disease Chronic kidney disease Chronic total occlusion Percutaneous coronary intervention Hemodialysis
a b s t r a c t Background: This study aimed to assess the prognosis and deleterious effects of chronic kidney disease (CKD) on future renal function, in patients who had undergone chronic total occlusion-percutaneous coronary intervention (CTO-PCI). Methods: The treatment effects were studied in 739 patients who underwent CTO-PCI. The patients were divided into 3 groups according to estimated glomerular filtration rate (eGFR): non-CKD (eGFR ≥ 60 ml/min/1.73m2, n = 562), CKD-1 (45 ≤ eGFR b 60 ml/min/1.73m2, n = 90), and CKD-2 (eGFR b 45 ml/min/1.73m2, n = 87). Future hemodialysis (HD) rates and the prevalence of acute kidney injury (AKI) except for 45 patients undergoing regular HD, and other clinical and prognostic outcomes were compared between the 3 groups. Results: Procedural success rates showed trends toward lower prevalence across the 3 groups (89.5%, 84.4%, and 81.6%, p = 0.060). The prevalence of AKI significantly differed between the 3 groups (4.6%, 8.9%, and 16.7%, p = 0.001), whereas no patients were introduced to regular HD at discharge. During a median follow-up period of 51.2 ± 28.9 months, newly required HD significantly differed between the 3 groups (0.7%, 0%, and 7.1%, p b 0.001). When compared with unsuccessful CTO-PCI, successful CTO-PCI was found to improve cardiovascular mortality in the non-CKD and CKD-1 (Log-rank test: p = 0.025, p = 0.024, respectively) and to improve both cardiovascular and all-cause mortality in the CKD-2 (Log-rank test: p = 0.027, p = 0.0022, respectively). Conclusions: Although CTO-PCI for patients with advanced CKD was associated with a high risk of future HD introduction, not directly owing to CTO-PCI and AKI, successful treatment of CTO might contribute to better survival benefit regardless of the presence or absence of CKD. © 2016 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Recanalization of chronic total occlusion (CTO) by percutaneous coronary intervention (PCI) still remains a challenge in terms of technique and uncertainty of clinical advantages. The beneficial effects of this treatment is difficult to evaluate objectively, whereas studies evaluating the effects of CTO-PCI on prognosis, have reported that prognosis im⁎ Corresponding authors at: Department of Cardiovascular Medicine, Toyohashi Heart Center, 21-1, Gobudori, Ohyama-cho, Toyohashi, Aichi 441-8530, Japan. E-mail addresses: [email protected] (M. Yamamoto), [email protected] (E. Tsuchikane).
http://dx.doi.org/10.1016/j.ijcard.2016.08.019 0167-5273/© 2016 Elsevier Ireland Ltd. All rights reserved.
proved indirectly or consistently in the successful CTO treatment group as compared to the failure of CTO treatment group [1–5]. Patient backgrounds and lesion characteristics are important factors for the successful treatment of CTO. Patients with renal dysfunction are especially likely to be found in the failure group because of its lesion complexity. Patients with chronic kidney disease (CKD) who were undergoing invasive treatments were generally associated with poorer prognosis than patients without CKD [4–8]. Therefore, presence or absence of CKD, and the severity of disease may have an influence on prognosis, regardless of success or failure of CTO-PCI. CKD is a general term for heterogeneous disorders affecting kidney function. Few studies have investigated the clinical outcomes between CKD grading and CTO-PCI.
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Patients with CKD may have less benefits depending on their CKD severity, even though CTO-PCI was successfully performed. In addition, little is known regarding the clinical concerns of introduction of regular hemodialysis (HD) at acute and late phase in these cohorts. Therefore, we retrospectively studied the deleterious effects of CKD and its severity on clinical outcomes including serial renal function change in patients who underwent CTO-PCI. 2. Methods 2.1. Patient population Consecutive patients who underwent CTO-PCI were extracted from the database of the Toyohashi Heart Center, Toyohashi, Japan, in which data were entered prospectively. In this retrospective study, pretreatment and posttreatment clinical data were collected from a single-center PCI registry. The database included relevant patient information and angiographic and procedural characteristics. For this study 7353 PCI procedures performed between January 2006 and December 2013 were screened, of which 848 involved revascularization of a CTO. Patients who underwent CTOs in more than one vessel or lesions in a small coronary branch vessel, and those in whom a repeat procedure succeeded an initial failure were excluded from the study, as were the few patients who were untraceable. We excluded patients with CTO lesions in more than one vessel in order to evaluate the effect of a single CTO-PCI recanalization and those with small-branch lesions because of the known lesser clinical advantage in such cases. The remaining 739 patients represented the total study population. The patients include, who underwent CTO-PCI were divided into 3 groups according to estimated glomerular filtration rate (eGFR). Patients with eGFR ≥60 ml/min/1.73 m2 were classified in the non-CKD group; those with 45 ml/min/1.73 m2 ≤ eGFR b60 ml/min/1.73 m2 in the CKD-1 group; and those with eGFR b45 ml/min/1.73 m2, in the CKD-2 group. eGFR was calculated according to the CKD guidelines proposed by the Japanese Society of Nephrology on the based on the modified Modification of Diet in Renal Disease equation [9]. 2.2. Definitions Coronary CTO was defined as a true total occlusion with complete interruption of antegrade blood flow as assessed by using coronary arteriography (thrombolysis in myocardial infarction [TIMI] flow grade 0) and with estimated occlusion duration of 3 months or longer. For the procedural background inherent in this study, we examined the total amount of contrast medium, procedure time, and radiation dose. Procedure time was defined as the total duration of the patient's stay in the catheterization room (from entry until exit). Fluoroscopy time and radiation dose were recorded automatically by the cine device. Coronary perforation was examined as a possible complication of the procedure. These information were corrected from our single-center PCI registry database as we previously reported [10]. The registry data included the total amount of contrast media, procedure time, and radiation dose during all CTO procedures. The following endpoints were evaluated to compare patients in whom the procedure failed and those in whom the procedure was successful: all-cause death and evident cardiac death. Evident cardiac death was defined as heart failure, myocardial infarction (MI), or unexpected death presumed to be due to ischemic cardiovascular disease and arrhythmia that occurred within 24 h after the onset of symptoms, without clinical or postmortem evidence of another cause,
and this was judged according to the information from the telephonic interview with the patient and patient's family. Death from uncertain causes was also classified as cardiac death. Double CTO was defined as the presence of a CTO lesion in more than one vessel at the same time. Procedural success was defined as residual stenosis of ≤50% with TIMI flow grade 3 and without major adverse cardiovascular events. Periprocedural MI was diagnosed based on an increase in creatinine kinase level to twice the upper limit of normal. The definition of acute kidney injury (AKI) was modified by using the Kidney Disease Improving Global Outcomes Guidelines definition as follows: ≥0.3 mg/dl at discharge after the procedure or ≥50% increase in serum creatinine level from its baseline value to its post–cardiac catheterization peak level at any time during hospitalization [11]. Baseline creatinine level was defined as the most recent serum creatinine level measured prior to the procedure. Acute Kidney Injury Network stage 2 (AKIN2) was defined as a doubling in the baseline serum creatinine level or the development of a new dialysis-dependent renal failure [12].
2.3. Data acquisition Clinical data from all the patients with CTO lesions treated invasively were prospectively recorded in a computerized database as a single-center PCI registry [10]. The recorded data included patient status, clinical characteristics, laboratory data, presence of concomitant diseases, characteristics of CTO lesions, angiographic findings, revascularization procedure, and in-hospital mortality. Whether HD was required during the follow-up period was also evaluated based on individual patient charts. The mean follow-up period was 51.2 ± 28.9 months. These strategies made it possible to collect data.
2.4. Invasive treatment and medications All the patients were treated with elective PCI because of stable angina or asymptomatic myocardial ischemia. The patients received aspirin (100 mg) and ticlopidine (200 mg) or clopidogrel (75 mg) daily before the intervention. Other medications were continued during hospitalization. Patients with CKD-2 and CKD-3 group received hydration to prevent the occurrence of AKI before the CTO procedure. The hydration regimens were administered according to previous recommendations: isotonic sodium chloride solution or lactate ringer solution were started with an infusion rate of 1 ml/kg of body weight per hour 12 h before and (continued 12 h) after procedure. However, the hydration volume control varied in each patient due to the presence of multiple co-morbidities such as age, renal function and ejection fraction.
2.5. Statistical analyses The primary outcome of this study was all-cause mortality after PCI. Results are presented as mean, SD, or numbers and percentages. The study groups were compared by using one-way analysis of variance for continuous variables and χ2 test. Long-term outcomes were presented by using Kaplan-Meier survival curves and compared by using the log-rank test. Data with p values b 0.05 were considered statistically significant. Univariate logistic regression analysis was performed to evaluate the associations between the clinical parameters and AKI. Thereafter, multivariate analysis was performed the factors in univariate analysis with p-value b 0.05 to assess their independent association of AKI after procedure.
Table 1 Baseline patient characteristics in CKD group allocation. Baseline patient characteristics in CKD group allocation
Non-CKD (eGFR ≧ 60) n = 562
CKD-1 group (45 ≦ eGFR b 60) n = 90
CKD-2 group (eGFR b 45) n = 87
P value
Age, yrs ≧80 yrs Male Diabetes mellitus Hypertension Hyperlipidemia Prior CABG Prior PCI Prior CI Smoking Family history Body weight, kg Body height, m Body mass index (BMI) Laboratory data Creatinine (mg/dL) Blood urea nitrogen (mg/dL) eGFR (ml/min/1.73m2) Patient with hemodialysis
64.6 ± 10.7 40 (7.1%) 485 (86.3%) 60 (10.7%) 329 (58.5%) 241 (42.9%) 56 (10.0%) 17 (3.0%) 160 (28.5%) 154 (27.4%) 89 (15.8%) 65.3 ± 12.6 163.1 ± 8.0 24.4 ± 3.7
71.4 ± 9.1 18 (20.0%) 67 (74.4%) 10 (11.1%) 51 (56.7%) 33 (36.7%) 12 (13.3%) 0 (0%) 28 (31.1%) 14 (15.6%) 10 (11.1%) 62.5 ± 10.5 160.6 ± 8.2 24.1 ± 3.0
68.6 ± 10.6 19 (21.8%) 64 (73.6%) 17 (19.5%) 58 (66.7%) 20 (23.0%) 8 (9.2%) 3 (3.4%) 33 (37.9%) 8 (9.2%) 7 (8.0%) 60.7 ± 12.4 161.3 ± 8.9 23.1 ± 3.8
b0.001 b0.001 0.001 0.057 0.31 0.002 0.58 0.23 0.19 b0.001 0.101 0.001 0.09 0.012
0.83 ± 0.15 15.4 ± 4.0 83.4 ± 16.9 0 (0%)
1.13 ± 0.14 19.9 ± 5.5 54.0 ± 4.0 0 (0%)
5.49 ± 3.8 37.4 ± 14.6 19.7 ± 16.7 45 (51.7%)
b0.001 b0.001 b0.001 b0.001
Values are n (%) or mean ± SD. CABG, Coronary artery bypass grafting; PCI, Percutaneous coronary intervention; CI, Cerebral infarction; eGFR, estimated glomerular filtration rate.
T. Shimura et al. / International Journal of Cardiology 222 (2016) 707–713
3. Results 3.1. Baseline and procedural characteristics The baseline patient characteristics significantly differed between the 3 groups (Table 1). Approximately half of the patients in CKD-2 group (45/87, 51.7%) were undergoing regular HD before receiving CTO-PCI. Patient age, sex, and body characteristics, including weight and body mass index, showed significant differences between the 3 groups. The baseline lesion and procedural characteristics are presented in Table 2. The prevalence rates of severe calcified lesion, use of a rotablator for recanalization, and use of intra-aortic balloon pumping were significantly higher across the 3 groups (p b 0.001, p b 0.001, and p b 0.001, respectively). These results were considered to reflect the lesion and procedural complexity in advanced-stage CKD. As a result, procedural success rates showed trends toward lower prevalence rates across the 3 groups (89.5% vs. 84.4% vs. 81.6%, p = 0.060). The operators reduced the use of contrast medium in the patient groups with higher renal impairment (303.6 ± 153.3 ml vs. 268.9 ± 161.4 ml vs.
709
211.9 ± 120.8 ml, p b 0.001). Procedural time and complications such as dissection and coronary perforation did not differ between the 3 groups. In the CKD-2 group, 45 patients were excluded from the analysis concerning the prevalence of AKI and new hemodialysis introduction after CTO-PCI. The prevalence of AKI stage 1 was significantly higher in the CKD-2 group than in the other two groups (26/562 [4.6%] vs. 8/ 90 [8.9%] vs. 7/42 [16.7%], p = 0.001]. AKI stage 2 occurred only in one patient in the CKD-1 group (0/562 [0%] vs. 1/90 [1.1%] vs. 0/42 [0%], p = 0.001), and none of the patients had AKI stage 3. Logistic regression analysis for the relationship between the clinical factors and AKI are shown in Table 3. Presence of CKD and contrast volume were independent predictors of the increasing risk of AKI (OR = 2.40, 95% confidence interval [CI] = 1.53–3.76, p b 0.001; and OR = 1.002, 95% CI = 1.00– 1.004, p = 0.022; respectively). None of the patients in CKD-2 group was introduced to regular HD at discharge. Moreover, none of the patients enrolled in this study were introduced to regular HD at discharge. Two patients with AKI stage 1 were finally introduced to regular HD during the follow-up period. However, the patient with AKI stage 2 did not need regular HD during the follow-
Table 2 Baseline lesion and procedural characteristics. Baseline lesion and procedural characteristics Location of CTO RCA LAD LCx LMT Lesion characteristics In stent occlusion Ulceration Irregularity Eccentricity Bifurcation at CTO site Calcification None, Mild Moderate Severe Tortuosity None, Mild Moderate Severe Legion Length b10 mm 10 mm ≦ b 20 mm 20 mm ≦ Use of Rotablator Use of IABP Success rate Dilatation strategies (success case only) Non stent use BMS use DES use Complications Coronary dissection No coronary dissection Dissection with flow limitation Dissection without flow limitation Coronary perforation No coronary perforation Perforation type 1 Perforation type 2 Procedure time (min) Contrast volume (ml) Acute Kidney Injury AKI stage 1 AKI stage 2 AKI stage 3 Newly required hemodialysis At discharge At follow-up period
Non-CKD (eGFR ≧ 60) n = 562
CKD-1 group (45 ≦ eGFR b 60) n = 90
CKD-2 group (eGFR b 45) n = 87
281 (50.0%) 168 (29.9%) 112 (19.9%) 1 (0.2%)
34 (37.8%) 30 (33.3%) 23 (25.6%) 3 (3.3%)
43 (49.4%) 21 (24.1%) 23 (26.4%) 0 (0%)
61 (10.9%) 4 (0.7%) 10 (1.8%) 256 (45.6%) 107 (19.0%)
12 (13.3%) 1 (1.1%) 2 (2.2%) 34 (37.8%) 23 (25.6%)
14 (16.1%) 0 (0%) 3 (3.4%) 40 (46.0%) 13 (14.9%)
0.33 0.65 0.58 0.37 0.19
377 (67.1%) 135 (24.0%) 50 (8.9%)
55 (61.1%) 28 (31.1%) 7 (7.8%)
32 (36.8%) 29 (33.3%) 26 (29.9%)
b0.001
432 (76.9%) 97 (17.3%) 33 (5.9%)
69 (76.7%) 14 (15.6%) 7 (7.8%)
64 (73.6%) 16 (18.4%) 7 (8.0%)
0.88
3 (0.5%) 94 (16.7%) 465 (82.7%) 38 (6.8%) 11 (2.0%) 503 (89.5%)
3 (3.3%) 12 (13.3%) 75 (83.3%) 3 (3.3%) 6 (6.7%) 76 (84.4%)
3 (3.4%) 17 (19.5%) 67 (77.0%) 18 (20.7%) 10 (11.5%) 71 (81.6%)
0/503 (0%) 17/503 (3.4%) 486/503 (96.6%)
0/76 (0%) 4/76 (5.3%) 72/76 (94.7%)
0/71 (0%) 2/71 (2.8%) 69/71 (97.2%)
0.67
512 (91.1%) 2 (0.4%) 48 (8.5%)
82 (91.1%) 1 (1.1%) 7 (7.8%)
77 (88.5%) 0 (0%) 10 (11.5%)
0.66
497 (88.4%) 62 (11.0%) 3 (0.5%) 189.4 ± 90.2 303.6 ± 153.3
77 (85.6%) 12 (13.3%) 1 (1.1%) 197.3 ± 92.0 268.9 ± 161.4
79 (90.8%) 8 (9.2%) 0 (0%) 188.1 ± 87.0 211.9 ± 120.8
0.72 b0.001
26 (4.6%) 0 (0%) 0 (0%)
8 (8.9%) 1 (1.1%) 0 (0%)
7/42 (16.7%) 0/42 (0%) 0/42 (0%)
0.001 0.001 N0.99
0 (0%) 4 (0.7%)
0 (0%) 0 (0%)
0/42 (0%) 3/42 (7.1%)
N0.99 b0.001
P value
0.002
0.035 b0.001 b0.001 0.060
0.77
Values are n (%) or mean ± SD. CTO, Chronic total occlusion; RCA, Right coronary artery; LAD, Left anterior descending coronary artery; LCx, Left circumflex coronary artery; LMT, Left main trunk coronary artery; IABP, Intra-aortic balloon pumping; BMS, Bare metal stent; DES, Drug eluting stent; AKI, acute kidney injury.
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Table 3 Odds ratio analysis for the association between patient/lesion characteristics and acute kidney injury. Univariate analysis Adjusting factors Baseline clinical characteristics Age (per 1 year increase) Male (for female) Body mass index (per 1 m2 increase) Diabetes mellitus Hypertension Hyperlipidemia Chronic kidney disease (per 1 group increase) Baseline lesion and procedural characteristics In stent occlusion (for no in stent occlusion) Ulceration (for no ulceration) Irregularity (for no irregularity) Eccentricity (for no eccentricity) Bifurcation at CTO site Calcification (per 1 category increase) Tortuosity (per 1 category increase) Legion Length (per 1 category increase) Post procedural variables Procedure success (for failure) Procedure time (min) Contrast volume (ml)
Multivariate analysis
Odds ratio
95% confidence interval
p value
Odds ratio
95% confidence interval
p value
1.04 0.49 1.02 1.75 1.59 0.99 2.08
1.004–1.07 0.54–3.66 0.94–1.11 0.75–4.09 0.81–3.11 0.52–1.86 1.36–3.16
0.093 0.49 0.62 0.20 0.18 0.97 0.001
2.23
1.40–3.55
b0.001
0.81 0.00 1.42 0.77 1.95 1.44 1.36 1.09
0.28–2.33 0.00 0.18–11.3 0.41–1.47 0.98–3.86 0.94–2.21 0.85–2.20 0.59–2.40
0.70 0.99 0.74 0.43 0.056 0.097 0.20 0.83
0.51 1.004 1.002
0.23–1.15 1.001–1.007 1.001–1.004
0.10 0.008 0.007
1.002 1.002
1.00–1.006 1.00–1.004
0.29 0.022
CTO, Chronic total occlusion.
up period. The prevalence of newly required HD during the follow-up period significantly differed between the 3 groups (4/562 [0.7%] vs. 0/ 91 [0%] vs. 3/43 [7.0%], respectively; p b 0.001). 3.2. Long-term mortality During a median follow-up of 51.2 ± 28.9 months after discharge, 85 of the 739 patients died during the follow-up period. Of these, 56 patients died from a cardiovascular event. Details on the clinical outcomes of the 7 patients who were newly introduced to HD are presented in Table 4. Although 4 of the 7 patients died during the follow-up period, the causes of their deaths were thought to be associated with multiple factors beyond renal failure itself. Of the 4 patients, none died immediately after the introduction of HD. Only 2 of the 7 patients developed AKI stage 1 after the CTO procedure. One of them was in the CKD-2 group and introduced to regular HD 828 days after CTO-PCI. Another patient who belonged to the non-CKD group was introduced to regular HD 72 days after the PCI procedure. To begin with, the time from the PCI procedure to regular HD introduction differed greatly between the 7 patients (range, 72–2299 days). The cumulative mortality rates in each of the 3 CKD stages were compared for the 2 different groups between CTO-PCI success and failure by using Kaplan-Meier curves. The all-
cause mortality in the non-CKD group showed no significant difference between the success and failure groups (log-rank test: p = 0.45). Meanwhile, the cardiovascular mortality in the success group was significantly lower than that in the failure group (p = 0.025; Fig. 1-A, B). Similar results regarding all-cause mortality (p = 0.23) and cardiovascular mortality (p = 0.024) were found in the CKD-1 group between the success and failure groups (Fig. 2-A, B). By contrast, the patients in the CKD2 group who had a successful PCI were associated with better clinical outcomes in terms of both all-cause and cardiovascular mortality than those who had a failed PCI (p = 0.027 and p = 0.0022, respectively; Fig. 3-A, B). 4. Discussion The results of the present study demonstrated two major findings. First, successful CTO-PCI, when compared with failed CTO-PCI, significantly improved the cardiovascular mortality of the patients in the non-CKD and CKD-1 groups (45 ml/min/1.73 m2 ≤ eGFR b60 ml/min/ 1.73 m2). Furthermore, it improved the all-cause and cardiovascular mortality of the patients in the advanced CKD-2 group (eGFR b45 ml/min/1.73 m2). Previous research proved that the prognosis in the successful CTO treatment group was better than that in the failed
Table 4 Patient characteristics of newly required hemodialysis after CTO-PCI. Patient age Gender
eGFR
Creatinine (baseline)
Creatinine (discharge)
Procedure time
Contrast volume
AKI
Procedure success
Time from procedure to HD
Follow-up period
Outcomes Cause of death
53 years Male 79 years Male 64 years Male 75 years Female 73 years Male 68 years Male 70 years Male
136.7 ml/min/1.73m2
0.56 mg/dl
0.60 mg/dl
195 min
320 ml
(−)
(+)
2299 days
2299 days
Alive
76.8 ml/min/1.73m2
0.86 mg/dl
1.50 mg/dl
265 min
374 ml
Stage1
(+)
72 days
213 days
69.8 ml/min/1.73m
2
0.97 mg/dl
0.94 mg/dl
220 min
180 ml
(−)
(+)
856 days
1133 days
67.2 ml/min/1.73m
2
0.75 mg/dl
1.00 mg/dl
340 min
350 ml
(−)
(+)
1768 days
2612 days
Death heart failure Death septic shock Alive
37.1 ml/min/1.73m2
1.64 mg/dl
1.96 mg/dl
122 min
65 ml
Stage 1
(+)
828 days
1042 days
32.5 ml/min/1.73m2
1.86 mg/dl
1.99 mg/dl
189 min
400 ml
(−)
(+)
1640 days
1956 days
2
4.09 mg/dl
2.82 mg/dl
175 min
120 ml
(−)
(+)
102 days
1658 days
13.0 ml/min/1.73m
eGFR, estimated glomerular filtration rate; HD, hemodialysis; AKI, acute kidney injury.
Death heart failure Alive Death critical limb ischemia
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Fig. 1. A Kaplan-Meier curve showing differences in all-cause mortality between successful and failed CTO-PCI in the non-CKD group. There were no statistical differences between successful and failed CTO-PCI in The non-CKD group patients. B Kaplan-Meier curve showing differences in cardiovascular mortality between successful and failed CTO-PCI in the nonCKD group. Successful CTO-PCI in the non-CKD group patients was associated with a decrease in cardiovascular mortality compared to the failed CTO-PCI group.
CTO treatment group [1–5]. In addition, CKD was associated with increased mortality after CTO-PCI [4,5]. It remains uncertain whether patients with an advanced CKD stage would receive the clinical benefits of CTO-PCI depending on the severity of their CKD, even though CTO-PCI is successfully performed. Invasive CTO-PCI for patients with advanced CKD stage is generally considered challenging. In fact, a trend toward low success rates of CTO-PCI was found in the advanced CKD group with severe calcified lesions. However, the beneficial outcomes of successful CTO-PCI as compared with an unsuccessful procedure were not attenuated after the subdivision of the CKD stages. This was especially emphasized in the patients with severely reduced kidney function (eGFR b 45 ml/min/1.73 m2). Recent large-scale data revealed a steep increase in the risk for cardiovascular mortality in advanced CKD groups and underlined the importance of the subdivision of CKD groups by using a threshold eGFR of 45 ml/min/1.73 m2 for each CKD stage [13, 14]. The present results also revealed that the cumulative mortality rates in the CKD-2 group regardless of success or failure of the CTOPCI were higher than those in the non-CKD and CKD-1 groups. If CTOPCI were to be performed in such patients with advanced CKD, operators should understand the poor prognosis in this cohort and continue efforts to improve their technical skills in the recanalization of the artery with CTO.
Second, this study provides data on the prevalence rates of newly required HD in a CTO-PCI cohort. Excessive procedure time and amount of contrast medium were needed during the complex CTO-PCI in some cases. The physicians therefore hesitated in performing CTO-PCI for these patients with advanced CKD when they were concerned about the increased risk of procedure-related kidney injury. Our study also revealed advanced CKD class and contrast volume were independent risk factors of AKI as previous investigations demonstrated [8,10]. The operators tried to reduce the volume of contrast media in the advanced CKD groups, the mean dose of contrast medium used was 200 ml more than that used in conventional PCI [15]. Nevertheless, in such a negative situation, only 42 patients (5.7%) developed AKI; and none of them was introduced to regular HD until the discharge period. Moreover, only 2 patients developed AKI and were finally introduced to regular HD during the follow-up period. One of them belonged to the non-CKD group. He had blue toe syndrome after percutaneous peripheral intervention 2 months after the CTO procedure. His serum creatinine level increased from 0.97 mg/dL to 4.15 mg/dL after the procedure, which led to the introduction of regular HD. The other patient was from the CKD-2 group and was introduced to regular HD 828 days after the CTO procedure because of the natural history of CKD. These results may suggest that the occurrence of AKI does not directly relate to an
Fig. 2. A Kaplan-Meier curve showing differences in all-cause mortality between successful and failed CTO-PCI in the non-CKD group. There were no statistical differences between successful and failed CTO-PCI in the CKD-1 group patients. B Kaplan-Meier curve showing differences in cardiovascular mortality between successful and failed CTO-PCI in the nonCKD group. Successful CTO-PCI in the CKD-1 group patients was associated with a decrease in cardiovascular mortality compared to the failed CTO-PCI group.
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Fig. 3. A Kaplan-Meier curve showing differences in all-cause mortality between successful and failed CTO-PCI in the non-CKD group. Successful CTO-PCI in CKD-2 group patients was associated with a decrease in all-cause mortality compared to failed CTO-PCI group. B Kaplan-Meier curve showing differences in cardiovascular mortality between successful and failed CTO-PCI in the non-CKD group. Successful CTO-PCI in the CKD-2 group patients was associated with a decrease in cardiovascular mortality compared to the failed CTO-PCI group.
early- and late-phase HD introduction. The actual prevalence rates of late-phase HD introduction in the 3 groups were 0.7%, 0%, and 7%, respectively. The higher prevalence of future HD introduction in the patients with eGFR of b45 ml/min/1.73 m2 should be highlighted, whereas these results were quite comparable with those of other conventional invasive procedures [16]. In addition, time from procedure to HD introduction widely ranged from 72 to 2299 days, depending on the background differences between the 7 patients, as partially mentioned earlier. Of these patients, 4 died, although not immediately after HD introduction. The interval between new HD introduction and date of death was quite long (minimum, 213 days). The causes of death, such as heart failure, septic shock, or critical limb ischemia, were not considered to be directly due to renal failure itself. The above-mentioned findings might be informative for decision making in CTO-PCI for patients with advanced CKD, when taking into account the risk-benefit balance.
However, the risk of AKI and future HD introduction in the advanced CKD group was notable, although none of the patients was introduced to maintenance HD immediately after the procedure. Therefore, successful treatment of CTO might contribute to better survival benefit regardless of the presence or absence of CKD. Funding sources None. Disclosures None. Conflict of interest statement There are no conflicts of interest to declare.
4.1. Study limitations References This study has several limitations. First, the success of CTO-PCI is highly dependent on the physician's technique and experience. Although our hospital's experience in performing CTO-PCI has accumulated, the results in acute successful cases may differ under conditions with less physician experience. Second, as this is a retrospective observational study, it has inherent limitations. Third, 45 of the 87 patients in the CKD-2 group were already undergoing maintenance HD. No statistical differences in clinical outcomes were found between the patients with HD in the CKD-2 group (n = 45) and those in the non-HD group (n = 42) in this study. A sample volume of 40 patients divided into success and failure groups was not enough to provide the additional information. A large number of patients would be required to prove the clinical outcomes of CTO-PCI under classified CKD staging. Therefore, we cannot overstate our study conclusions. Finally, the majority of enrolled patients in our study are Japanese. Recent report revealed that cardiovascular disease risk differed in subjects with CKD by races [17]. When considered the race differences, the current results might not be similar. 5. Conclusions Successful CTO-PCI, compared with failed CTO-PCI, significantly improved the cardiovascular mortality of the patients in the non-CKD and mild CKD groups. Furthermore, it improved the all-cause and cardiovascular mortality of the patients in the advanced CKD group.
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