CRISPR-Cas9-guided amplification-free genomic diagnosis for familial hypercholesterolemia using nanopore sequencing.

Familial hypercholesterolemia is an inherited disorder that remains underdiagnosed. Conventional genetic testing methods such as next-generation sequencing (NGS) or target PCR are based on the amplification process. Due to the efficiency limits of polymerase and ligase enzymes, these methods usually target short regions and do not detect large mutations straightforwardly. This study combined the long-read nanopore sequencing and CRISPR-Cas9 system to sequence the target DNA molecules without amplification. We originally designed and optimized the CRISPR-RNA panel to target the low-density lipoprotein receptor gene (LDLR) and proprotein convertase subtilisin/kexin type 9 gene (PCSK9) from human genomic DNA followed by nanopore sequencing. The average coverages for LDLR and PCSK9 were 106× and 420×, versus 1.2× for the background genome. Among them, continuous reads were 52x and 307x, respectively, and spanned the entire length of LDLR and PCSK9. We identified pathogenic mutations in both coding and splicing donor regions in LDLR. We also detected an 11,029 bp large deletion in another case. Furthermore, using continuous long reads generated from the benchmark experiment, we demonstrated how a false-positive 670 bp deletion caused by PCR amplification errors was easily eliminated.

Successful Management of Malignant Pericarditis Using Nivolumab for Metastatic Esophageal Squamous Cell Carcinoma.

Esophageal cancer is a malignant disease with a poor prognosis and is one of the most common causes of cardiac metastasis. Malignant pericarditis may cause the repetitive accumulation of pericardial effusion, which can occasionally pose a clinical challenge. We herein report a case of malignant pericarditis in a patient with metastatic esophageal squamous cell carcinoma with cardiac tamponade, which was successfully managed with single pericardial drainage and systemic nivolumab monotherapy. This is the first case report to suggest that systemic therapy with nivolumab is a promising option for the management of malignant pericarditis.

Can Machine Learning Aid the Selection of Percutaneous vs Surgical Revascularization?

BACKGROUND: In patients with 3-vessel coronary artery disease (CAD) and/or left main CAD, individual risk prediction plays a key role in deciding between percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). OBJECTIVES: The aim of this study was to assess whether these individualized revascularization decisions can be improved by applying machine learning (ML) algorithms and integrating clinical, biological, and anatomical factors. METHODS: In the SYNTAX (Synergy between PCI with Taxus and Cardiac Surgery) study, ML algorithms (Lasso regression, gradient boosting) were used to develop a prognostic index for 5-year death, which was combined, in the second stage, with assigned treatment (PCI or CABG) and prespecified effect-modifiers: disease type (3-vessel or left main CAD) and anatomical SYNTAX score. The model's discriminative ability to predict the risk of 5-year death and treatment benefit between PCI and CABG was cross-validated in the SYNTAX trial (n = 1,800) and externally validated in the CREDO-Kyoto (Coronary REvascularization Demonstrating Outcome Study in Kyoto) registry (n = 7,362), and then compared with the original SYNTAX score II 2020 (SSII-2020). RESULTS: The hybrid gradient boosting model performed best for predicting 5-year all-cause death with C-indexes of 0.78 (95% CI: 0.75-0.81) in cross-validation and 0.77 (95% CI: 0.76-0.79) in external validation. The ML models discriminated 5-year mortality better than the SSII-2020 in the external validation cohort and identified heterogeneity in the treatment benefit of CABG vs PCI. CONCLUSIONS: An ML-based approach for identifying individuals who benefit from CABG or PCI is feasible and effective. Implementation of this model in health care systems-trained to collect large numbers of parameters-may harmonize decision making globally. (Synergy Between PCI With TAXUS and Cardiac Surgery: SYNTAX Extended Survival [SYNTAXES]; NCT03417050; SYNTAX Study: TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries; NCT00114972).

Statin Discontinuation After Coronary Revascularization.

There is a scarcity of studies evaluating statin discontinuation in patients with coronary artery disease in real-world practice. In 11,144 patients who underwent first coronary revascularization and taking statins in the CREDO-Kyoto Registry Cohort-3, we evaluated the incidence of statin discontinuation, defined as stopping statins for at least 2 months. The reasons for statin discontinuation included nonadherence, side effects, worsening co-morbidities, surgery, prescription error, and direction by physicians for other reasons. During a median 6 years of follow-up, the cumulative incidence of statin discontinuation was 6.1% at 1 year, 12.4% at 3 years, 17.4% at 5 years, and 21.4% at 7 years. The major components of the reasons for statin discontinuation were nonadherence, side effects, and worsening co-morbidities. Compared with patients with statin discontinuation because of other reasons, patients with statin discontinuation because of nonadherence more often had younger age, men, acute coronary syndrome, and current smoking; patients with statin discontinuation because of side effects more often had liver cirrhosis; and patients with statin discontinuation because of worsening co-morbidities more often had advanced age and co-morbidities such as malignancy. Statin discontinuation was strongly associated with subsequent mortality (hazard ratio [HR] 3.54; 95% confidence interval [CI] 3.18 to 3.94, p <0.001), which was consistent, regardless of the reasons, except for the small group of patients with prescription error (nonadherence: HR 2.35, 95% CI 1.69 to 3.27, p <0.001; side effects: HR 2.48, 95% CI 1.84 to 3.34, p <0.001; worsening co-morbidities: HR 22.08, 95% CI 18.55 to 26.29, p <0.001). In conclusion, in real-world practice, approximately 1 in 5 patients discontinued statins after coronary revascularization during a median of 6 years of follow-up. Statin discontinuation was associated with subsequent mortality.

Polypharmacy and Bleeding Outcomes After Percutaneous Coronary Intervention.

BACKGROUND: Polypharmacy was reported to be associated with major bleeding in various populations. However, there are no data on polypharmacy and its association with bleeding in patients undergoing percutaneous coronary intervention (PCI).Methods and Results: Among 12,291 patients in the CREDO-Kyoto PCI Registry Cohort-3, we evaluated the number of medications at discharge and compared major bleeding, defined as Bleeding Academic Research Consortium Type 3 or 5 bleeding, across tertiles (T1-3) of the number of medications. The median number of medications was 6, and 88.0% of patients were on ≥5 medications. The cumulative 5-year incidence of major bleeding increased incrementally with increasing number of medications (T1 [≤5 medications] 12.5%, T2 [6-7] 16.5%, and T3 [≥8] 20.4%; log-rank P<0.001). After adjusting for confounders, the risks for major bleeding of T2 (hazard ratio [HR] 1.21; 95% confidence interval [CI] 1.08-1.36; P=0.001) and T3 (HR 1.27; 95% CI 1.12-1.45; P<0.001) relative to T1 remained significant. The adjusted risks of T2 and T3 relative to T1 were not significant for a composite of myocardial infarction or ischemic stroke (HR 0.95 [95% CI 0.83-1.09; P=0.47] and HR 1.06 [95% CI 0.91-1.23; P=0.48], respectively). CONCLUSIONS: In a real-world population of patients undergoing PCI, approximately 90% were on ≥5 medications. Increasing number of medications was associated with a higher adjusted risk for major bleeding, but not ischemic events.

Post-contrast Acute Kidney Injury After Emergent and Elective Percutaneous Coronary Intervention (from the CREDO-Kyoto PCI/CABG Registry Cohort 3).

Post-contrast acute kidney injury (PC-AKI) is a common complication after percutaneous coronary intervention (PCI). However, it is unclear whether or not the effects of PC-AKI on long-term clinical outcomes were different between emergent and elective procedures. Among patients enrolled in the CREDO-Kyoto PCI/CABG (Coronary Revascularization Demonstrating Outcome Study in Kyoto Percutaneous Coronary Intervention/Coronary Artery Bypass Grafting) registry cohort 3, we identified 10,822 patients treated using PCI (emergent PCI stratum: n = 5,022 [46%] and elective PCI stratum: n = 5,860 [54%]). PC-AKI was defined as ≥0.3 mg/100 ml absolute or 1.5-fold relative increase of serum creatinine within 72 hours after PCI. The incidence of PC-AKI was significantly higher after emergent PCI than after elective PCI (10.5% vs 3.7%, p <0.001). In the multivariable logistic regression model, emergent PCI was the strongest independent risk factor for PC-AKI in the entire study population. The excess adjusted risk of patients with PC-AKI relative to those without remained significant for all-cause death in both the emergent and elective PCI strata (hazard ratio 1.87, 95% confidence interval 1.59 to 2.21, p <0.001 and hazard ratio 1.31, 95% confidence interval 1.03 to 1.68, p = 0.03, respectively). There was a significant interaction between the PCI setting (emergent and elective) and the effect of PC-AKI on all-cause death, with a greater magnitude of effect in the emergent PCI stratum than in the elective PCI stratum (p for interaction = 0.01). In conclusion, the incidence of PC-AKI was 2.8 times higher after emergent PCI than after elective PCI. The excess mortality risk of PC-AKI relative to no PC-AKI was greater after emergent PCI than after elective PCI.

Association between cancer history and second-generation drug-eluting stent thrombosis: insights from the REAL-ST registry.

BACKGROUND: Cancer-associated thrombosis is a frequent complication of cancer; however, little evidence is available regarding the association between cancer history and coronary artery stent thrombosis (ST). We aimed to investigate the relationship between cancer history and second-generation drug-eluting stent thrombosis (G2-ST). METHODS: From the REAL-ST (Retrospective Multicenter Registry of ST After First- and Second-Generation Drug-Eluting Stent Implantation) registry, this study evaluated 1265 patients (G2- ST cases, n = 253; controls, n = 1012) with cancer-related information available. RESULTS: The prevalence of patients with cancer history was higher (12.3% vs. 8.5%, p = 0.065), and that of currently diagnosed and currently treated cancer was significantly higher in ST cases than controls (3.6% vs. 1.4%, p = 0.021; 3.2% vs. 1.3%, p = 0.037, respectively). Multivariable logistic regression analysis revealed that cancer history was associated with late ST (odds ratio [OR]: 2.80, 95% confidence intervals [CI]: 0.92-8.55, p = 0.071) and very late ST (OR: 2.40, 95% CI: 1.02-5.65, p = 0.046), but not with early ST (OR: 1.01, 95% CI: 0.51-2.00, p = 0.97). During the median follow-up period of 872 days after the index ST events, patients with cancer history showed a higher mortality than those without, among both ST cases (hazard ratio [HR]: 1.93, 95% CI: 1.06-3.51, p = 0.031) and controls (HR: 1.93, 95% CI: 1.09-3.40, p = 0.023). CONCLUSION: A post hoc analysis of REAL-ST registry revealed that patients with G2-ST had a higher prevalence of currently diagnosed and currently treated cancer. Notably, cancer history was associated with the occurrence of late and very late ST, but not with early ST.

Life Expectancy of Patients With Severe Aortic Stenosis in Relation to Age and Surgical Risk Score.

BACKGROUND: There is a paucity of data regarding shorter life expectancy after aortic valve replacement (AVR) in patients with severe aortic stenosis (AS). METHODS: Among 3815 patients with severe AS enrolled in the CURRENT AS (Contemporary outcomes after sURgery and medical tREatmeNT in patients with severe Aortic Stenosis) registry, there were 1469 patients (initial AVR: n = 647; conservative strategy: n = 822) with low surgical risk, 1642 patients (initial AVR: n = 433; conservative strategy: n = 1209) with intermediate surgical risk, and 704 patients (initial AVR: n = 117; conservative strategy: n = 587) with high surgical risk. Among 1163 patients who actually underwent surgical AVR as the initial strategy, patients were divided into 4 groups according to age <65 years (n = 185), 65 to 74 (n = 394), 75 to 80 (n = 345), and >80 (n = 239). The expected survival of the general Japanese population was obtained from the Statistics Bureau of Japan. The surgical risk was estimated using The Society of Thoracic Surgery (STS) score. RESULTS: The median follow-up was 3.7 years. The cumulative incidences of all-cause death were significantly lower in the initial AVR strategy than in the initial conservative strategy across the 3 STS groups. Shorter life expectancy after surgical AVR was seen especially in younger patients. The observed mortality in low-risk patients was comparable to the expected mortality across all the age-groups, while intermediate-risk patients aged <75 years, and high-risk patients across all age-groups had higher mortality compared with the expected mortality. CONCLUSIONS: The risk stratification according to age and STS score might be useful to estimate shorter life expectancy after AVR, and these findings have implications for decision making in the choice of surgical or transcatheter AVR.

Sex Differences in Clinical Outcomes After Percutaneous Coronary Intervention.

BACKGROUND: There is a scarcity of studies comparing the clinical outcomes after percutaneous coronary intervention (PCI) for women and men stratified by the presentation of acute coronary syndromes (ACS) or stable coronary artery disease (CAD).Methods and Results: The study population included 26,316 patients who underwent PCI (ACS: n=11,119, stable CAD: n=15,197) from the CREDO-Kyoto PCI/CABG registry Cohort-2 and Cohort-3. The primary outcome was all-cause death. Among patients with ACS, women as compared with men were much older. Among patients with stable CAD, women were also older than men, but with smaller difference. The cumulative 5-year incidence of all-cause death was significantly higher in women than in men in the ACS group (26.2% and 17.9%, log rank P<0.001). In contrast, it was significantly lower in women than in men in the stable CAD group (14.2% and 15.8%, log rank P=0.005). After adjusting confounders, women as compared with men were associated with significantly lower long-term mortality risk with stable CAD but not with ACS (hazard ratio [HR]: 0.75, 95% confidence interval [CI]: 0.69-0.82, P<0.001, and HR: 0.92, 95% CI: 0.84-1.01, P=0.07, respectively). There was a significant interaction between the clinical presentation and the mortality risk of women relative to men (interaction P=0.002). CONCLUSIONS: Compared with men, women had significantly lower adjusted mortality risk after PCI among patients with stable CAD, but not among those with ACS.

Percutaneous coronary intervention using new-generation drug-eluting stents versus coronary arterial bypass grafting in stable patients with multi-vessel coronary artery disease: From the CREDO-Kyoto PCI/CABG registry Cohort-3.

AIMS: There is a scarcity of studies comparing percutaneous coronary intervention (PCI) using new-generation drug-eluting stents (DES) with coronary artery bypass grafting (CABG) in patients with multi-vessel coronary artery disease. METHODS AND RESULTS: The CREDO-Kyoto PCI/CABG registry Cohort-3 enrolled 14927 consecutive patients who underwent first coronary revascularization with PCI or isolated CABG between January 2011 and December 2013. The current study population consisted of 2464 patients who underwent multi-vessel coronary revascularization including revascularization of left anterior descending coronary artery (LAD) either with PCI using new-generation DES (N = 1565), or with CABG (N = 899). Patients in the PCI group were older and more often had severe frailty, but had less complex coronary anatomy, and less complete revascularization than those in the CABG group. Cumulative 5-year incidence of a composite of all-cause death, myocardial infarction or stroke was not significantly different between the 2 groups (25.0% versus 21.5%, P = 0.15). However, after adjusting confounders, the excess risk of PCI relative to CABG turned to be significant for the composite endpoint (HR 1.27, 95%CI 1.04-1.55, P = 0.02). PCI as compared with CABG was associated with comparable adjusted risk for all-cause death (HR 1.22, 95%CI 0.96-1.55, P = 0.11), and stroke (HR 1.17, 95%CI 0.79-1.73, P = 0.44), but with excess adjusted risk for myocardial infarction (HR 1.58, 95%CI 1.05-2.39, P = 0.03), and any coronary revascularization (HR 2.66, 95%CI 2.06-3.43, P<0.0001). CONCLUSIONS: In this observational study, PCI with new-generation DES as compared with CABG was associated with excess long-term risk for major cardiovascular events in patients who underwent multi-vessel coronary revascularization including LAD.

Unravelling the Difference Between Men and Women in Post-CABG Survival.

Objectives: Women have a worse prognosis after coronary artery bypass grafting (CABG) surgery compared to men. We sought to quantify to what extent this difference in post-CABG survival could be attributed to sex itself, or whether this was mediated by difference between men and women at the time of intervention. Additionally, we explored to what extent these effects were homogenous across patient subgroups. Methods: Time to all-cause mortality was available for 102,263 CABG patients, including 20,988 (21%) women, sourced through an individual participant data meta-analysis of five cohort studies. Difference between men and women in survival duration was assessed using Kaplan-Meier estimates, and Cox's proportional hazards model. Results: During a median follow-up of 5 years, 13,598 (13%) patients died, with women more likely to die than men: female HR 1.20 (95%CI 1.16; 1.25). We found that differences in patient characteristics at the time of CABG procedure mediated this sex effect, and accounting for these resulted in a neutral female HR 0.98 (95%CI 0.94; 1.02). Next we performed a priori defined subgroup analyses of the five most prominent mediators: age, creatinine, peripheral vascular disease, type 2 diabetes, and heart failure. We found that women without peripheral vascular disease (PVD) or women aged 70+, survived longer than men (interaction p-values 0.04 and 6 × 10-5, respectively), with an effect reversal in younger women. Conclusion: Sex differences in post-CABG survival were readily explained by difference in patient characteristics and comorbidities. Pre-planned analyses revealed patient subgroups (aged 70+, or without PVD) of women that survived longer than men, and a subgroup of younger women with comparatively poorer survival.

Rationale, Design, and Baseline Characteristics of the CURRENT AS Registry-2.

BACKGROUND: There is scarce data evaluating the current practice pattern and clinical outcomes for patients with severe aortic stenosis (AS), including both those who underwent surgical aortic valve replacement (SAVR) or transcatheter aortic valve implantation (TAVI) and those who were managed conservatively in the TAVI era.Methods and Results: The Contemporary outcomes after sURgery and medical tREatmeNT in patients with severe Aortic Stenosis (CURRENT AS) Registry-2 is a prospective, physician-initiated, multicenter registry enrolling consecutive patients who were diagnosed with severe AS between April 2018 and December 2020 among 21 centers in Japan. The rationale for the prospective enrollment was to standardize the assessment of symptomatic status, echocardiographic evaluation, and other recommended diagnostic examinations such as computed tomography and measurement of B-type natriuretic peptide. Moreover, the schedule of clinical and echocardiographic follow up was prospectively defined and strongly recommended for patients who were managed conservatively. The entire study population consisted of 3,394 patients (mean age: 81.6 years and women: 60%). Etiology of AS was degenerative in 90% of patients. AS-related symptoms were present in 60% of patients; these were most often heart failure symptoms. The prevalence of high- and low-gradient AS was 58% and 42%, respectively, with classical and paradoxical low-flow low-gradient AS in 4.6% and 6.7%, respectively. CONCLUSIONS: The CURRENT AS Registry-2 might be large and meticulous enough to determine the appropriate timing of intervention for patients with severe AS in contemporary clinical practice.

Coronary Artery Disease Without Standard Cardiovascular Risk Factors.

Recently, one observational study showed that patients with ST-segment elevation myocardial infarction (STEMI) without standard cardiovascular risk factors were associated with increased mortality compared with patients with risk factors. This unexpected result should be evaluated in other populations including those with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and chronic coronary syndrome (CCS). Among 30,098 consecutive patients undergoing first coronary revascularization in the CREDO-Kyoto PCI/CABG (Coronary Revascularization Demonstrating Outcome Study in Kyoto Percutaneous Coronary Intervention/Coronary Artery Bypass Grafting) registry cohort-2 and 3, we compared clinical characteristics and outcomes between patients with and without risk factors stratified by their presentation (STEMI n = 8,312, NSTE-ACS n = 3,386, and CCS n = 18,400). Patients with risk factors were defined as having at least one of the following risk factors: hypertension, dyslipidemia, diabetes, and current smoking. The proportion of patients without risk factors was low (STEMI: 369 patients [4.4%], NSTE-ACS: 110 patients [3.2%], and CCS: 462 patients [2.5%]). Patients without risk factors compared with those with risk factors more often had advanced age, low body weight, and malignancy and less often had history of atherosclerotic disease and prescription of optimal medical therapy. In patients with STEMI, patients without risk factors compared with those with risk factors were more often women and more often had atrial fibrillation, long door-to-balloon time, and severe hemodynamic compromise. During a median of 5.6 years follow-up, patients without risk factors compared with those with risk factors had higher crude incidence of all-cause death. After adjusting confounders, the mortality risk was significant in patients with CCS (hazard ratio [HR] 1.22, 95% confidence interval [CI] 1.01 to 1.49, p = 0.04) but not in patients with STEMI (HR 1.06, 95% CI 0.89 to 1.27, p = 0.52) and NSTE-ACS (HR 1.07, 95% CI, 0.74 to 1.54, p = 0.73). In conclusion, among patients undergoing coronary revascularization, patients without standard cardiovascular risk factors had higher crude incidence of all-cause death compared with those with at least one risk factor. After adjusting confounders, the mortality risk was significant in patients with CCS but not in patients with STEMI and NSTE-ACS.

Effect of Polypharmacy on Long-Term Mortality After Percutaneous Coronary Intervention.

Polypharmacy was reported to be associated with increased mortality in various populations. However, there is a scarcity of data on status of polypharmacy and association with long-term mortality in patients who underwent percutaneous coronary intervention (PCI). Among 12,291 patients who underwent first PCI in the CREDO-Kyoto PCI/CABG registry Cohort-3, we evaluated the number of medications at discharge from index PCI hospitalization, and compared long-term mortality across the 3 groups divided by the tertiles of the number of medications. The median number of medications was 6 (interquartile range: 5 to 8), and 88.0% of the patients were on >=5 medications. Most of medications were those related to cardiovascular disease. Patients taking more medications were older and more often had co-morbidities and guideline-indicated medications. The cumulative 5-year incidence of all-cause death increased incrementally with increasing number of medications (Tertile 1 [<=5]: 13.1%, Tertile 2 [6 to 7]: 13.9%, and Tertile 3 [>=8]: 18.0%, log-rank p <0.001). After adjusting confounders, the mortality risks of Tertile 2 and Tertile 3 relative to Tertile 1 were no longer significant (Tertile 2: hazard ratio 0.93; 95% confidence interval 0.84 to 1.04; p = 0.23, and Tertile 3: hazard ratio 0.91; 95% confidence interval 0.81 to 1.03; p = 0.14, respectively). In conclusion, in a real-world population of patients who underwent PCI, approximately 90% of patients were on >=5 medications. Increasing medications was associated with higher crude incidence of all-cause death, whereas adjusted mortality risks were similar regardless of the number of medications. These data might suggest that achievement of optimal medical therapy would be preferred, even if it might increase the number of medications used.

External Validation of the SYNTAX Score II 2020.

BACKGROUND: The SYNTAX score II 2020 (SSII-2020) was derived from cross correlation and externally validated in randomized trials to predict death and major adverse cardiac and cerebrovascular events (MACE) following percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) in patients with 3-vessel disease (3VD) and/or left main coronary artery disease (LMCAD). OBJECTIVES: The authors aimed to investigate the SSII-2020's value in identifying the safest modality of revascularization in a non-randomized setting. METHODS: Five-year mortality and MACE were assessed in 7,362 patients with 3VD and/or LMCAD enrolled in a Japanese PCI/CABG registry. The discriminative abilities of the SSII-2020 were assessed using Harrell's C statistic. Agreement between observed and predicted event rates following PCI or CABG and treatment benefit (absolute risk difference [ARD]) for these outcomes were assessed by calibration plots. RESULTS: The SSII-2020 for 5-year mortality well predicted the prognosis after PCI and CABG (C-index = 0.72, intercept = -0.11, slope = 0.92). When patients were grouped according to the predicted 5-year mortality ARD, <4.5% (equipoise of PCI and CABG) and ≥4.5% (CABG better), the observed mortality rates after PCI and CABG were not significantly different in patients with lower predicted ARD (observed ARD: 2.1% [95% CI: -0.4% to 4.4%]), and the significant difference in survival in favor of CABG was observed in patients with higher predicted ARD (observed ARD: 9.7% [95% CI: 6.1%-13.3%]). For MACE, the SSII-2020 could not recommend a specific treatment with sufficient accuracy. CONCLUSIONS: The SSII-2020 for predicting 5-year death has the potential to support decision making on revascularization in patients with 3VD and/or LMCAD.

Coronary Revascularization in the Past Two Decades in Japan (From the CREDO-Kyoto PCI/CABG Registries Cohort-1, -2, and -3).

The treatment of coronary artery disease has substantially changed over the past two decades. However, it is unknown whether and how much these changes have contributed to the improvement of long-term outcomes after coronary revascularization. We assessed trends in the demographics, practice patterns and long-term outcomes in 24,951 patients who underwent their first percutaneous coronary intervention (PCI) (n = 20,106), or isolated coronary artery bypass grafting (CABG) (n = 4,845) using the data in a series of the CREDO-Kyoto PCI/CABG Registries (Cohort-1 [2000 to 2002]: n = 7,435, Cohort-2 [2005 to 2007]: n = 8,435, and Cohort-3 [2011 to 2013]: n = 9,081). From Cohort-1 to Cohort-3, the patients got progressively older across subsequent cohorts (67.0 ± 10.0, 68.4 ± 9.9, and 69.8 ± 10.2 years, ptrend < 0.001). There was increased use of PCI over CABG (73.5%, 81.9%, and 85.2%, ptrend < 0.001) and increased prevalence of evidence-based medications use over time. The cumulative 3-year incidence of all-cause death was similar across the 3 cohorts (9.0%, 9.0%, and 9.3%, p = 0.74), while cardiovascular death decreased over time (5.7%, 5.1%, and 4.8%, p = 0.03). The adjusted risk for all-cause death and for cardiovascular death progressively decreased from Cohort-1 to Cohort-2 (HR:0.89, 95%CI:0.80 to 0.99, p = 0.03, and HR:0.80, 95%CI:0.70 to 0.92, p = 0.002, respectively), and from Cohort-2 to Cohort-3 (HR:0.86, 95%CI:0.78 to 0.95, p = 0.004, and HR:0.77, 95%CI:0.67-0.89, p < 0.001, respectively). The risks for stroke and repeated coronary revascularization also improved over time. In conclusions, we found a progressive and substantial reduction of adjusted risk for all-cause death, cardiovascular death, stroke, and repeated coronary revascularization over the past two decades in Japan.

Effect of Heart Failure on Long-Term Clinical Outcomes After Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting in Patients With Severe Coronary Artery Disease.

Background Heart failure might be an important determinant in choosing coronary revascularization modalities. There was no previous study evaluating the effect of heart failure on long-term clinical outcomes after percutaneous coronary intervention (PCI) relative to coronary artery bypass grafting (CABG). Methods and Results Among 14 867 consecutive patients undergoing first coronary revascularization with PCI or isolated CABG between January 2011 and December 2013 in the CREDO-Kyoto PCI/CABG registry Cohort-3, we identified the current study population of 3380 patients with three-vessel or left main coronary artery disease, and compared clinical outcomes between PCI and CABG stratified by the subgroup based on the status of heart failure. There were 827 patients with heart failure (PCI: N=511, and CABG: N=316), and 2553 patients without heart failure (PCI: N=1619, and CABG: N=934). In patients with heart failure, the PCI group compared with the CABG group more often had advanced age, severe frailty, acute and severe heart failure, and elevated inflammatory markers. During a median 5.9 years of follow-up, there was a significant interaction between heart failure and the mortality risk of PCI relative to CABG (interaction P=0.009), with excess mortality risk of PCI relative to CABG in patients with heart failure (HR, 1.75; 95% CI, 1.28-2.42; P<0.001) and no excess mortality risk in patients without heart failure (HR, 1.04; 95% CI, 0.80-1.34; P=0.77). Conclusions There was a significant interaction between heart failure and the mortality risk of PCI relative to CABG with excess risk in patients with heart failure and neutral risk in patients without heart failure.

Comparison of Outcomes of Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting Among Patients With Three-Vessel Coronary Artery Disease in the New-Generation Drug-Eluting Stents Era (From CREDO-Kyoto PCI/CABG Registry Cohort-3).

There is a scarcity of data comparing long-term clinical outcomes between percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) in patients with three-vessel coronary artery disease (3VD) in the new-generation drug-eluting stents era. CREDO-Kyoto PCI/CABG registry Cohort-3 enrolled 14927 consecutive patients who had undergone first coronary revascularization with PCI or isolated CABG between January 2011 and December 2013. We identified 2525 patients with 3VD (PCI: n = 1747 [69%], and CABG: n = 778 [31%]). The primary outcome measure was all-cause death. Median follow-up duration was 5.7 (interquartile range: 4.4 to 6.6) years. The cumulative 5-year incidence of all-cause death was significantly higher in the PCI group than in the CABG group (19.8% vs 13.2%, log-rank p = 0.001). After adjusting confounders, the excess risk of PCI relative to CABG for all-cause death remained significant (HR, 1.45; 95% CI, 1.14 to 1.86; p = 0.003), which was mainly driven by the excess risk for non-cardiovascular death (HR, 1.88; 95% CI, 1.30 to 2.79; p = 0.001), while there was no excess risk for cardiovascular death between PCI and CABG (HR, 1.19; 95% CI, 0.87 to 1.64; p = 0.29). There was significant excess risk of PCI relative to CABG for myocardial infarction (HR, 1.77; 95% CI, 1.19 to 2.69; p = 0.006), whereas there was no excess risk of PCI relative to CABG for stroke (HR, 1.24; 95% CI, 0.83 to 1.88; p = 0.30). In conclusion, in the present study population reflecting real-world clinical practice in Japan, PCI compared with CABG was associated with significantly higher risk for all-cause death, while there was no excess risk for cardiovascular death between PCI and CABG.

Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting in Patients With Versus Without Chronic Kidney Disease.

Chronic kidney disease (CKD) might be an important determinant in choosing percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). However, there is a scarcity of studies evaluating the effect of CKD on long-term outcomes after PCI relative to CABG in the population including severe CKD. Among 30257 consecutive patients patients who underwent first coronary revascularization with PCI or isolated CABG in the CREDO-Kyoto PCI/CABG registry Cohort-2 (n = 15330) and Cohort-3 (n = 14,927), we identified the current study population of 12,878 patients with multivessel or left main disease, and compared long-term clinical outcomes between PCI and CABG stratified by the subgroups based on the stages of CKD (no CKD: eGFR >=60 ml/min/1.73m2, moderate CKD: 60> eGFR >=30 ml/min/1.73m2, and severe CKD: eGFR <30 ml/min/1.73m2 or dialysis). There were 6,999 patients without CKD (PCI: n = 5,268, and CABG: n = 1,731), 4,427 patients with moderate CKD (PCI: n = 3,226, and CABG: n = 1,201), and 1,452 patients with severe CKD (PCI: n = 989, and CABG: n = 463). During median 5.6 years of follow-up, the excess mortality risk of PCI relative to CABG was significant regardless of the stages of CKD without interaction (no CKD: HR, 1.36; 95%CI, 1.12 to 1.65; p = 0.002, moderate CKD: HR, 1.40; 95%CI, 1.17 to 1.67; p <0.001, and severe CKD: HR, 1.33; 95%CI, 1.09 to 1.62; p = 0.004, Interaction p = 0.83). There were no significant interactions between CKD and the effect of PCI relative to CABG for all the outcome measures evaluated. In conclusion, PCI compared with CABG was associated with significantly higher risk for all-cause death regardless of the stages of CKD without any significant interaction.