Elevated levels of plasma inactive stromal cell derived factor-1α predict poor long-term outcomes in diabetic patients following percutaneous coronary intervention.

BACKGROUND: Since the complication of diabetes mellitus (DM) is a risk for adverse cardiovascular outcomes in patients with coronary artery disease (CAD), appropriate risk estimation is needed in diabetic patients following percutaneous coronary intervention (PCI). However, there is no useful biomarker to predict outcomes in this population. Although stromal cell derived factor-1α (SDF-1α), a circulating chemokine, was shown to have cardioprotective roles, the prognostic impact of SDF-1α in diabetic patients with CAD is yet to be fully elucidated. Moreover, roles of SDF-1α isoforms in outcome prediction remain unclear. Therefore, this study aimed to assess the prognostic implication of three forms of SDF-1α including total, active, and inactive forms of SDF-1α in patients with DM and after PCI. METHODS: This single-center retrospective analysis involved consecutive patients with diabetes who underwent PCI for the first time between 2008 and 2018 (n = 849). Primary and secondary outcome measures were all-cause death and the composite of cardiovascular death, non-fatal myocardial infarction, and ischemic stroke (3P-MACE), respectively. For determining plasma levels of SDF-1α, we measured not only total, but also the active type of SDF-1α by ELISA. Inactive isoform of the SDF-1α was calculated by subtracting the active isoform from total SDF-1α. RESULTS: Unadjusted Kaplan-Meier analyses revealed increased risk of both all-cause death and 3P-MACE in patients with elevated levels of inactive SDF-1α. However, plasma levels of total and active SDF-1α were not associated with cumulative incidences of outcome measures. Multivariate Cox hazard analyses repeatedly indicated the 1 higher log-transformed inactive SDF-1α was significantly associated with increased risk of all-cause death (hazard ratio (HR): 2.64, 95% confidence interval (CI): 1.28-5.34, p = 0.008) and 3P-MACE (HR: 2.51, 95% CI: 1.12-5.46, p = 0.02). Moreover, the predictive performance of inactive SDF-1α was higher than that of total SDF-1α (C-statistics of inactive and total SDF-1α for all-cause death: 0.631 vs 0.554, for 3P-MACE: 0.623 vs 0.524, respectively). CONCLUSION: The study results indicate that elevated levels of plasma inactive SDF-1α might be a useful indicator of poor long-term outcomes in diabetic patients following PCI. TRIAL REGISTRATION: This study describes a retrospective analysis of a prospective registry database of patients who underwent PCI at Juntendo University Hospital, Tokyo, Japan (Juntendo Physicians' Alliance for Clinical Trials, J-PACT), which is publicly registered (University Medical Information Network Japan-Clinical Trials Registry, UMIN-CTR 000035587).

Favorable Prognosis in Patients with Recovered Pulmonary Hypertension after TAVI: An Analysis of the LAPLACE-TAVI Registry.

Pulmonary hypertension (PH) is a common complication of aortic stenosis (AS). Despite the established association between PH and poor outcomes in patients with AS, the prognostic implication of a change in PH after transcatheter aortic valve implantation (TAVI) has been rarely evaluated. This study analyzed a prospective multi-center TAVI registry database involving six Japanese centers and used the transtricuspid pressure gradient (TRPG) obtained by echocardiography to estimate pulmonary artery systolic pressure. The participants (n = 2056) were first divided into two groups by TRPG before TAVI, a PH (−) group (TRPG < 30 mmHg) (n = 1407, 61.9%) and a PH (+) group (TRPG ≥ 30 mmHg) (n = 649, 28.6%). Next, by TRPG after (4.1 ± 5.3 days) TAVI, the PH (+) group was further subdivided into two groups, Recovered PH (TRPG < 30 mmHg, n = 253) and Persistent PH (TRPG after TAVI ≥ 30 mmHg, n = 396). The median follow-up duration was 1.8 years. The primary and secondary endpoints were the composite and each of cardiovascular (CV) death and heart failure hospitalization, respectively. Unadjusted Kaplan-Meier estimates with log-rank comparisons showed significantly higher cumulative incidences of primary and secondary endpoints in the Persistent PH group compared to other groups. Moreover, adjusted multivariate Cox-proportional hazard analyses showed that a decreased (−10 mmHg) TRPG after TAVI was linearly associated with a reduced risk of the primary endpoint (hazard ratio (HR): 0.76, 95% confidence interval (CI): 0.64−0.90, p = 0.0020). The findings in the present study indicate that the recovery of PH may partly contributes to the prognostic benefit of TAVI procedure in patients with AS and elevated pulmonary artery systolic pressure.

Low apolipoprotein A1 was associated with increased risk of cancer mortality in patients following percutaneous coronary intervention: A 10-year follow-up study.

Previous studies showed that elevated apolipoprotein A1 (ApoA1) and high-density lipoprotein cholesterol (HDL-C) predicted reduced risk of cardiovascular-related (CV) mortality in patients following percutaneous coronary intervention (PCI). Nevertheless, as the association between ApoA1 and cancer mortality in this population has been rarely addressed, our study aimed to evaluate prognostic impact of ApoA1 on multiple types of cancer mortality after PCI. This is a retrospective analysis of a single-center prospective registry database of patients who underwent PCI between 2000 and 2018. The present study enrolled 3835 patients whose data of serum ApoA1 were available and they were divided into three groups according to the tertiles of the preprocedural level of ApoA1. The outcome measures were total, gastrointestinal, and lung cancer mortalities. The median and range of the follow-up period between the index PCI and latest follow-up were 5.9 and 0-17.8 years, respectively. Consequently, Kaplan-Meier analyses showed significantly higher rates of the cumulative incidences of total, gastrointestinal, and lung cancer mortality in the lowest ApoA1 tertile group compared to those in the highest. In contrast, there were no significant differences in all types of cancer mortality rates in the groups divided by the tertiles of HDL-C. Multivariable Cox proportional hazard regression analysis adjusted by cancer-related prognostic factors, such as smoking status, identified the elevated ApoA1 as an independent predictor of decreased risk of total and gastrointestinal cancer mortalities. Our study demonstrates the prognostic implication of preprocedural ApoA1 for predicting future risk of cancer mortality in patients undergoing PCI.

Dipeptidyl peptidase-4 inhibitors reduced long-term cardiovascular risk in diabetic patients after percutaneous coronary intervention via insulin-like growth factor-1 axis.

Dipeptidyl-peptidase-4 inhibitors (DPP4i) have been the most used antidiabetic medications worldwide due to their good safety profiles and tolerability with a low risk of hypoglycemia, however, large cardiovascular outcome trials (CVOTs) have not shown any significant the prognostic superiority. On the contrary, since observational studies have suggested the effects of DPP4i are enhanced some populations, such as Asians and those who without overweight, their prognostic benefit is still under debate. The aim of this study was thus to assess the prognostic impact of DPP4i in patients with both diabetes and coronary artery disease (CAD) who underwent percutaneous coronary intervention (PCI) through the insulin-like growth factor-1 (IGF-1) axis, a substrate of DPP4. This single-center analysis involved consecutive Japanese diabetic patients who underwent PCI for the first time between 2008 and 2018 (n = 885). Primary and secondary endpoints were set as cardiovascular (CV) death and the composite of CV death, non-fatal myocardial infarction and ischemic stroke (3P-MACE). Serum levels of IGF-1 and its main binding protein (insulin-like growth factor binding protein-3: IGFBP-3) were measured. In consequences, unadjusted Kaplan-Meier analyses revealed reduced incidences of CV-death and 3P-MACE by DPP4i, which was particularly enhanced in patients who were not overweight (BMI ≤ 25). Multivariate Cox hazard analyses consistently indicated reduced risks of CV death by DPP4i at PCI (hazard ratio (HR) 0.39, 95% confidence interval (CI) 0.16-0.82, p = 0.01) and 3P-MACE (HR 0.47, 95% CI 0.25-0.84, p = 0.01), respectively. Moreover, elevated IGF-1 activity indicated by the IGF-1/IGFBP-3 ratio was associated with decreased risks of both endpoints and it was significantly higher in patients with DPP4i (p < 0.0001). In conclusion, the findings of the present study indicate beneficial effects of DPP4i to improve outcomes in Japanese diabetic patients following PCI, which might be mediated by DPP4-IGF-1 axis.

A Prognostic Merit of Statins in Patients with Chronic Hemodialysis after Percutaneous Coronary Intervention-A 10-Year Follow-Up Study.

BACKGROUND: Patients with end-stage renal disease (ESRD) on chronic hemodialysis who are complicated by coronary artery disease (CAD) are at very high risk of cardiovascular (CV) events and mortality. However, the prognostic benefit of statins, which is firmly established in the general population, is still under debate in this particular population. METHODS: As a part of a prospective single-center percutaneous coronary intervention (PCI) registry database, this study included consecutive patients on chronic hemodialysis who underwent PCI for the first time between 2000 and 2016 (n = 201). Participants were divided into 2 groups by following 2 factors, such as (1) with or without statin, and (2) with or without high LDL-C (> and ≤LDL-C = 93 mg/dL, median) at the time of PCI. The primary endpoint was defined as CV death, and the secondary endpoints included all-cause and non-CV death, and 3 point major cardiovascular adverse events (3P-MACE) which is the composite of CV death, non-fatal myocardial infarction and stroke. The median and range of the follow-up period were 2.8, 0-15.2 years, respectively. RESULTS: Kaplan-Meier analyses showed significantly lower cumulative incidences of primary and secondary endpoints other than non-CV deaths in patients receiving statins. Conversely, no difference was observed when patients were divided by the median LDL-C at the time of PCI (p = 0.11). Multivariate Cox proportional hazard analysis identified statins as an independent predictor of reduced risk of CV death (Hazard ratio of statin use: 0.43, 95% confidence interval 0.18-0.88, p = 0.02), all-cause death (HR: 0.50, 95%CI 0.29-0.84, p = 0.007) and 3P-MACE (HR: 0.50, 95%CI 0.25-0.93, p = 0.03). CONCLUSIONS: Statins were associated with reduced risk of adverse outcomes in patients with ESRD following PCI.

The association between impairment of HDL cholesterol efflux capacity and atrial remodeling in atrial fibrillation.

This cross-sectional study enrolled 202 patients with atrial fibrillation (AF) who had undergone catheter ablation and evaluated the association between high-density lipoprotein (HDL) functionality, cholesterol efflux capacity (CEC) of HDL, and the pathophysiology of left atrial structural remodeling. Participants were divided into two groups, based on their left atrial volume index (LAVI) (< 34 mL/m2, n = 60 vs. LAVI ≥ 34 mL/m2, n = 142). We quantified three types of HDL CECs by the presence or absence of cyclic-AMP, as entire, and CEC dependent or not dependent on ATP binding cassette transporter A1 (ABCA1) and termed them Global CEC, ABCA1 CEC, and Non-ABCA1 CEC, respectively. Consequently, Global and Non-ABCA1 CECs were significantly impaired in patients with an enlarged LA (Global CEC: p = 0.039, Non-ABCA1 CEC: p = 0.022). Logistic regression analyses demonstrated that Non-ABCA1 CEC was significantly associated with an enlarged LA after adjusting for the conventional risk factors of AF. Furthermore, the association of higher Non-ABCA1 CEC with an enlarged LA was independent of serum levels of HDL cholesterol and serum myeloperoxidase (Odds ratio of 1 standard deviation higher: 0.64, 95% confidence interval: 0.43-0.95, p = 0.027). The findings of this study indicate the potential contribution of reduced Non-ABCA1 CEC in HDL to the pathophysiology in left atrial structural remodeling of patients with AF.

Low muscle mass assessed by psoas muscle area is associated with clinical adverse events in elderly patients with heart failure.

BACKGROUND: Acute decompensated heart failure (ADHF) is a growing healthcare burden with increasing prevalence and comorbidities due to progressive aging society. Accumulating evidence suggest that low skeletal muscle mass has a negative impact on clinical outcome in elderly adult population. We sought to determine the significance of psoas muscle area as a novel index of low skeletal muscle mass in elderly patients with ADHF. METHODS: In this single-center retrospective observational study, we reviewed consecutive 865 elderly participants (65 years or older) who were hospitalized for ADHF and 392 were available for analysis (79 years [74-85], 56% male). Cross-sectional areas of psoas muscle at the level of fourth lumbar vertebra were measured by computed tomography and normalized by the square of height to calculate psoas muscle index (PMI, cm2/m2). RESULTS: Dividing the patients by the gender-specific quartile value (2.47 cm2/m2 for male and 1.68 cm2/m2 for female), we defined low PMI as the lowest gender-based quartile of PMI. Multiple linear regression analysis revealed female sex, body mass index (BMI), and E/e', but not left ventricular ejection fraction, were independently associated with PMI. Kaplan-Meier analysis showed low PMI was associated with higher rate of composite endpoint of all-cause death and ADHF re-hospitalization (P = 0.033). Cox proportional hazard model analysis identified low PMI, but not BMI, was an independent predictor of the composite endpoint (Hazard ratio: 1.52 [1.06-2.16], P = 0.024). CONCLUSIONS: PMI predicted future clinical adverse events in elderly patients with ADHF. Further studies are needed to assess whether low skeletal muscle mass can be a potential therapeutic target to improve the outcome of ADHF.

Simultaneous Estimation of Gender Male and Atrial Fibrillation as Risk Factors for Adverse Outcomes Following Transcatheter Aortic Valve Implantation.

Accurate outcome prediction following transcatheter aortic valve implantation (TAVI) has gained further importance along with expanding its indication to patients with a lower surgical risk. Although previous studies have evaluated the prognostic impacts of gender and atrial fibrillation (AF) in TAVI patients, these two factors have rarely been addressed simultaneously. This retrospective observational study based on a multicenter TAVI registry involved 1088 patients who underwent TAVI between May, 2010 and February, 2020 at 3 hospitals in Japan. Participants were divided into 4 groups by gender and pre-existing AF, such as Female AF(-) (n = 559), Male AF(-) (n = 266), Female AF(+) (n = 187) and Male AF(+) (n = 76). Primary and secondary endpoints were death due to any and cardiovascular cause, and the composite of all-cause death and heart failure hospitalization, respectively. The median follow-up period was 538 days. Cumulative incidences of primary and secondary endpoints were lower in the Female AF(-) group compared to the other 3 groups. Adjusted multivariate Cox proportional hazard analyses showed an independent association of either or both of male gender and AF with adverse outcomes, when compared to the group with none of these (hazard ratios and 95% confidence intervals vs. Female AF(-) (reference) for all-cause death of Male AF(-): 2.7, 1.6-4.6, p < 0.001, Female AF(+): 3.5, 2.1-6.0, p < 0.001, and Male AF(+): 3.9, 1.9-7.8, p < 0.001), while there was no evidence of their synergistic prognostic impact. Male gender and being complicated by AF independently, but not synergistically, predicted poor long-term outcomes in patients undergoing TAVI.

Enhanced monocyte migratory activity in the pathogenesis of structural remodeling in atrial fibrillation.

BACKGROUND AND AIMS: Pathophysiological roles of monocytes in atrial fibrillation (AF), particularly for the progression of structural remodeling of the left atrium (LA), remain elusive. This study examined the association between the characteristics of circulating and local monocytes and extent of structural remodeling in LA, gauged by LA size, in AF patients. METHODS: First, 161 AF patients who were referred for catheter ablation were enrolled and divided into two groups according to the median of LA diameter (≤39 mm: normal LA group, >39 mm: enlarged LA group). As a control group, 22 patients underwent catheter ablation for paroxysmal supraventricular tachycardia (PSVT) without history of AF were analyzed. Blood samples were collected for flow cytometric analyses to evaluate monocyte subsets based on the levels of CD14 and CD16. Moreover, monocytes were isolated from blood to measure CC chemokine receptor 2 (CCR2) transcripts and protein levels, and migratory activity toward monocyte chemoattractant protein 1 (MCP-1). Second, to characterize the local monocytes in the atrial wall in AF, the resected left atrial appendages (LAA) in AF patients underwent cardiac surgery were histologically evaluated (n = 20). RESULTS: The proportions of monocyte subsets based on CD14 and CD16 expressions were not significantly different between the normal and enlarged LA group. Both transcripts and total protein levels of CCR2 in monocytes were higher in the enlarged LA group compared to those in the normal LA group. In the enlarged LA group, monocytes exhibited more enhanced migratory activity than the normal LA group. Moreover, we found a significantly higher number of CCR2-positive monocytes/macrophages in the LAA in the enlarged LA group. CONCLUSION: Enhanced migratory activity in circulating and local monocytes may play a pivotal role in the pathogenesis of progression in atrial remodeling in AF patients.

Residual Inflammation Indicated by High-Sensitivity C-Reactive Protein Predicts Worse Long-Term Clinical Outcomes in Japanese Patients after Percutaneous Coronary Intervention.

The aim of this study was to investigate the long-term clinical impact of residual inflammatory risk (RIR) by evaluating serial high-sensitivity C-reactive protein (hs-CRP) in Asian patients with coronary artery disease (CAD). We evaluated 2032 patients with stable CAD undergoing percutaneous coronary intervention (PCI) with serial hs-CRP measurements (2 measurements, 6-9 months apart) from the period 2000 to 2016. A high-RIR was defined as hs-CRP > 0.9 mg/L according to the median value. Patients were assigned to four groups: persistent-high-RIR, increased-RIR, attenuated-RIR, or persistent-low-RIR. Major adverse cardiac events (MACE) and all-cause death were evaluated. MACE rates in patients with persistent high, increased and attenuated RIR were significantly higher than in patients with persistent low RIR (p < 0.001). Moreover, the rate of all-cause death was significantly higher among patients with persistent high and increased RIR than among patients with attenuated and persistent low RIR (p < 0.001). After adjustment, the presence of persistent high RIR (hazard ratio (HR) 2.22; 95% confidence interval (CI) 1.37-3.67, p = 0.001), increased RIR (HR 2.25, 95%CI 1.09-4.37, p = 0.029), and attenuated RIR (HR 1.94, 95%CI 1.14-3.32, p = 0.015) were predictive for MACE. In addition, presence of persistent high RIR (HR 2.07, 95%CI 1.41-3.08, p < 0.001) and increased RIR (HR 1.94, 95%CI 1.07-3.36, p = 0.029) were predictive for all-cause death. A high RIR was significantly associated with MACE and all-cause death among Japanese CAD patients. An evaluation of changes in inflammation may carry important prognostic information and may guide the therapeutic approach.

Increased risk of cardiovascular mortality by strict glycemic control (pre-procedural HbA1c < 6.5%) in Japanese medically-treated diabetic patients following percutaneous coronary intervention: a 10-year follow-up study.

BACKGROUND: In the secondary prevention of cardiovascular (CV) disease in patients with diabetes, an optimal level of HbA1c, the most widely-used glycemic control indicator, for favorable clinical consequences still remains to be established. This study assessed the association between preprocedural HbA1c level and CV mortality in Japanese diabetic patients undergoing percutaneous coronary intervention (PCI). METHODS: This is a retrospective observational study using a single-center prospective PCI database involving consecutive 4542 patients who underwent PCI between 2000 and 2016. Patients with any antidiabetic medication including insulin at PCI were included in the analysis (n = 1328). We divided the patients into 5 and 2 groups according to HbA1c level; HbA1c: < 6.5% (n = 267), 6.5-7.0% (n = 268), 7.0-7.5% (n = 262), 7.5-8.5% (n = 287) and ≥ 8.5% (n = 244), and 7.0% > and ≤ 7.0%, respectively. The primary outcome was CV mortality including sudden death. The median follow-up duration was 6.2 years. RESULTS: In the follow-up period, CV and sudden death occurred in 81 and 23 patients, respectively. While unadjusted Kaplan-Meier analysis showed no difference in cumulative CV mortality rate between patients binarized by preprocedural HbA1c 7.0%, analysis of the 5 groups of HbA1c showed significantly higher cumulative CV death in patients with HbA1c < 6.5% compared with those with 7.0-7.5% (P = 0.042). Multivariate Cox hazard analysis revealed a U-shaped relationship between preprocedural HbA1c level and risk of CV death, and the lowest risk was in the HbA1c 7.0-7.5% group (Hazard ratio of HbA1c < 6.5% compared to 7.0-7.5%: 2.97, 95% confidence interval: 1.33-7.25, P = 0.007). Similarly, univariate analysis revealed the lowest risk of sudden death was in the HbA1c 7.0-7.5% group. CONCLUSION: The findings indicate an increased risk of CV mortality by strict glycemic control (HbA1c < 6.5%) in the secondary prevention of CV disease in Japanese patients with medically-treated diabetes. Trial registration This study reports the retrospective analysis of a prospective registry database of patients who underwent PCI at Juntendo University Hospital, Tokyo, Japan (Juntendo Physicians' Alliance for Clinical Trials, J-PACT), which is publicly registered (University Medical Information Network Japan-Clinical Trials Registry UMIN-CTR 000035587).

Prognostic impact of lipoprotein (a) on long-term clinical outcomes in diabetic patients on statin treatment after percutaneous coronary intervention.

BACKGROUND: Serum levels of lipoprotein (a) [Lp(a)] have been reported as a residual risk marker for adverse events in patients with coronary artery disease (CAD). However, the prognostic impact of Lp(a) on long-term clinical outcomes among diabetic patients on statin therapy after percutaneous coronary intervention (PCI) remains unclear. METHODS: The present investigation was a single-center, observational, retrospective cohort study. Among consecutive patients with CAD who underwent first PCI in our institution from 2000 to 2016, we enrolled diabetic patients on statin treatment. As a result, 927 patients (81% men; mean age, 67 years) were enrolled and divided into 2 groups according to a median Lp(a) level of 19.5 mg/dL. The incidence of major adverse cardiac events (MACE), including all-cause death, non-fatal myocardial infarction (MI), and non-fatal cerebral infarction (CI), was evaluated. RESULT: No significant differences were seen in age, sex, smoking habits, hypertension, chronic kidney disease, or body mass index between high and low Lp(a) groups. During follow-up (median, 5.0 years; interquartile range, 1.9-9.7 years), MACE occurred in 90 cases (17.6%), including 40 (7.9%) cardiac deaths, 18 (3.6%) non-fatal MI, and 37 (7.9%) non-fatal CI. Frequency of MACE was significantly higher in the high-Lp(a) group than in the low-Lp(a) group (log-rank test, p = 0.002). Higher Lp(a) level at the time of PCI was significantly associated with higher frequency of MACE, even after adjusting for other covariates, including other lipid profiles (hazard ratio, 1.91; 95% confidence interval, 1.20-3.09; p = 0.006). CONCLUSION: Our results demonstrated that in diabetic patients with CAD on statin treatment, increased Lp(a) levels could offer a good residual lipid risk marker. Assessing Lp(a) levels may be useful for risk stratification of long-term clinical outcomes after PCI, especially in diabetic patients.

Reduced Number of Platelets During Intra-Aortic Balloon Pumping Counterpulsation Predicts Higher Cardiovascular Mortality After Device Removal in Association with Systemic Inflammation.

Thrombocytopenia is a frequent complication in patients requiring intra-aortic balloon pumping (IABP) counterpulsation. However, its prognostic impact has not been fully addressed. The objective of this study is to evaluate the impact of the change in the platelet number during IABP use on the prognosis after device removal.This is a retrospective observational study. Patients in the intensive cardiac care unit at three Juntendo University hospitals who underwent percutaneous implantation of IABP with or without veno-arterial extracorporeal membrane oxygenation (V-A ECMO), since 2012-2016, were enrolled in the study (n = 439). Patients who died during mechanical circulatory support (n = 47) were excluded. We evaluated the prognostic impact of the ratio of platelet reduction from the baseline (% PLT reduction) during IABP use on cardiovascular mortality after device removal.The median and the range of follow-up period were 298 days and 0-1,869 days, respectively. Unadjusted Kaplan-Meier analysis demonstrated that patients with a higher % PLT reduction had higher cardiovascular (CV) mortality. An adjusted Cox proportional hazard analysis demonstrated that a 10% higher % PLT reduction was associated with higher cardiovascular (CV) mortality (Hazard ratio: 1.3, 95% Confidence interval: 1.1-1.6, P < 0.001). Moreover, % PLT reduction and the maximum C-reactive protein (CRP) level during IABP use were positively correlated (r = 0.326, P < 0.001).The reduced number of platelets during IABP use was associated with an increased risk of CV mortality.

Clinical impact of complex percutaneous coronary intervention in patients with coronary artery disease.

For the revascularization of patients with clinical and anatomical complexities, several technical skills are often required. However, the prognostic effect of complex percutaneous coronary intervention (C-PCI) on the clinical outcomes is not well known. The aim of this study was to investigate the relationship between the C-PCI and mid-term clinical outcomes. We assessed 1062 patients who underwent PCI with newer-generation drug-eluting stent and stratified the patients according to whether they had complex PCI (C-PCI, n = 358) or non-complex PCI (non-C-PCI, n = 704). C-PCI was defined as a procedure with at least 1 of the following features: 3 vessels treated, ≥ 3 stents per vessel implanted, ≥ 3 lesions treated, use of a 2-stent technique, the total stent length per vessel > 60 mm, chronic total occlusion, unprotected left main coronary artery stenting, and rotational atherectomy use. All-cause death and major adverse cardiac and cerebrovascular events (MACCE; cardiovascular death, non-fatal myocardial infarction, and non-fatal ischemic stroke) were evaluated. The median follow-up period was 1.9 (0.8-3.0) years. The baseline SYNTAX score was significantly higher in the C-PCI group than in the non-C-PCI group [20 (14-27) vs. 10 (6-17), p < 0.001]. Kaplan-Meier analysis showed that the cumulative incidences of all-cause death (log-rank p = 0.12) and MACCE (log-rank p = 0.64) did not differ between the two groups. On multivariable Cox analysis, C-PCI did not adversely affect the clinical outcomes. Despite a high rate of anatomically complex coronary lesions, the patients who underwent C-PCI had comparable "hard" clinical outcomes with those of non-C-PCI.

Clinical features of potential after-effects of percutaneous coronary intervention in the treatment of silent myocardial ischemia.

Clinical predictors for later adverse cardiovascular events in patients undergoing percutaneous coronary intervention (PCI) for silent myocardial ischemia remain undetermined. We investigated clinical features leading to later adverse cardiovascular events in patients who underwent PCI for silent myocardial ischemia. Of a total of 294 consecutive patients with a diagnosis of silent myocardial ischemia who successfully underwent contemporary PCI in our institute between January 2013 and December 2014, an initial event of any of all-cause death, hospitalized heart failure, acute coronary syndromes, and target vessel revascularization were identified as later adverse cardiovascular events and evaluated an association of them with baseline clinical characteristics. Silent myocardial ischemia was defined by an assessment of either electrocardiogram, myocardial perfusion imaging, coronary angiogram, or coronary fractional flow reserve. During a median follow-up of 565 days (interquartile range 361-816), later adverse cardiovascular events were identified in 38 patients (13%) consisting of 6 deaths, 5 hospitalized heart failures, 2 acute coronary syndromes, and 25 target vessel revascularizations. A presence of chronic kidney disease and/or insulin-treated diabetes mellitus, but not other clinical features, was strongly associated with later adverse cardiovascular events (hazard ratio 8.22; 95% confidential interval 2.95-29.25, P < 0.0001). Those events were increased in accordance with advanced stages of chronic kidney disease (P = 0.0003). A presence of chronic kidney disease and/or insulin-treated diabetes mellitus may lead the potential after-effects of PCI in the treatment of silent myocardial ischemia.

CPAP effects on atherosclerotic plaques in patients with sleep-disordered breathing and coronary artery disease: The ENTERPRISE trial.

BACKGROUND: Sleep-disordered breathing (SDB) is a novel cardiovascular risk factor. To date, the effects of continuous positive airway pressure (CPAP) on coronary plaque atheroma in SDB patients with coronary artery disease (CAD) have remained unclear. The CPAP Effects on Atherosclerotic Plaques in Patients with Sleep-Disordered Breathing and Coronary Artery Disease (ENTERPRISE) trial was designed to evaluate the effects of CPAP treatment in addition to optimal medical treatment on coronary plaque regression in SDB patients. METHODS: This study is planned as a prospective, randomized, open-label, single-center study. The presence of SDB is defined as a 3% oxygen desaturation index (ODI) of ≥15 events/h as measured by nocturnal pulse oximetry. A total of 100 eligible SDB patients undergoing intravascular ultrasound (IVUS)-guided percutaneous coronary intervention will be randomly assigned to either CPAP as add-on therapy or no CPAP for SDB (1:1 ratio for CPAP vs. no CPAP). The intervention will consist of 12 months of CPAP treatment. The primary endpoint will be percentage changes in plaque atheroma volume of the non-culprit lesion segment as measured by IVUS. A specialist sleep cardiology team will carefully monitor patients receiving CPAP treatment in order to quickly detect and resolve problems, and to motivate patients to continue treatment. CONCLUSION: This study will provide novel information on the effects of SDB and its treatment with CPAP on coronary plaque stability with regard to secondary prevention of CAD.

Long-Term Predictive Value of High-Sensitivity C-Reactive Protein for Cancer Mortality in Patients Undergoing Percutaneous Coronary Intervention.

BACKGROUND: High-sensitivity C-reactive protein (hs-CRP) is a well known risk factor for the development of cardiovascular disease and cancer. We investigated the long-term impact of hs-CRP on cancer mortality in patients with stable coronary artery disease (CAD). Methods and Results: This study was a retrospective analysis of 2,867 consecutive patients who underwent percutaneous coronary intervention for stable CAD from 2000 to 2016. The patients were divided into 2 groups according to median hs-CRP. We then evaluated the association between baseline hs-CRP and both all-cause and cancer deaths. Median hs-CRP was 0.10 mg/dL (IQR, 0.04-0.27 mg/dL). The median follow-up period was 5.8 years (IQR, 2.3-10.0 years). There were 416 deaths (14.5%), including 149 cardiovascular deaths (5.2%) and 115 (4.0%) cancer deaths. On Kaplan-Meier analysis the higher hs-CRP group had a significantly higher incidence of both all-cause and cancer death (log-rank, P<0.001 and P=0.001, respectively). On multivariable analysis higher hs-CRP was significantly associated with higher risk of cancer death (HR, 1.74; 95% CI: 1.18-2.61, P=0.005). CONCLUSIONS: Elevated baseline hs-CRP was significantly associated with cancer mortality in patients with stable CAD. Hs-CRP measurement may be useful for the identification of subjects with an increased risk of cancer death.

A novel and simply calculated nutritional index serves as a useful prognostic indicator in patients with coronary artery disease.

OBJECTIVE: No nutritional index has been firmly established yet in patients with coronary artery disease (CAD). In this study, we propose a simple to calculate nutritional indicator in patients who underwent percutaneous coronary intervention (PCI) by using parameters routinely measured in CAD and evaluated its prognostic implication. METHODS: This study is a retrospective observational analysis of a prospective database. The subjects were consecutive 3567 patients underwent their first PCI between 2000 and 2013 at Juntendo University Hospital in Tokyo. The median of the follow-up period was 6.3 years (range: 0-13.6 years). The novel nutritional index was calculated by the formula; Triglycerides (TG) × Total Cholesterol (TC) × Body Weight (BW) Index (TCBI) = TG × TC × BW / 1000 (TG and TC: mg/dl, and BW: kg). RESULTS: The Spearman non-parametric correlation coefficient between TCBI and the most often used conventional nutritional index, Geriatric Nutritional Risk Index (GNRI), was 0.355, indicating modest correlation. Moreover, Unadjusted Kaplan-Meier analysis showed higher all-cause mortality, cardiovascular mortality, and cancer mortality in patients with low TCBI. Consistently, elevation of TCBI was associated with reduced all-cause (hazard ratio: 0.86, 95%CI: 0.77-0.96, p < 0.001), cardiovascular (0.78, 0.66-0.92, p = 0.003), and cancer mortality (0.76, 0.58-0.99, p = 0.041) in patients after PCI by multivariate Cox proportional hazard analyses. CONCLUSION: TCBI, a novel and easy to calculate nutrition index, is a useful prognostic indicator in patients with CAD.