Subclinical myocardial damage after anthracycline chemotherapy in Japanese patients with breast cancer.

BACKGROUND: Data on the incidence, timing, and severity of myocardial damage after anthracycline-based chemotherapy (AC) in Japanese patients with breast cancer are limited. METHOD: We evaluated cancer therapy-related cardiac dysfunction (CTRCD) in Japanese women with breast cancer (n = 51) after the first AC according to the definitions of the 2022 European Society of Cardiology onco-cardiology guideline, including assessment of high-sensitivity troponin I (TnI) and B-type natriuretic peptide (BNP) levels. RESULTS: CTRCD was detected in 67 % of the patients (3.9 %, 7.8 %, 9.8 %, 43 %, 37 %, 22 %, 20 %, and 9.8 % of patients at 1 week and 1, 2, 3, 6, 9, 12, and 15 months post-AC, respectively) without significant left ventricular ejection fraction reduction (<50 %) and heart failure. Elevated TnI levels (>26 pg/mL) were found in 43 % of patients, and elevated BNP levels (≥35 pg/mL) were observed in 22 % of patients during the follow-up period. CONCLUSIONS: Approximately two-thirds of the Japanese patients in this study experienced CTRCD, which was frequently observed at 3 or 6 months post-AC. However, all patients with CTRCD were diagnosed with mild asymptomatic CTRCD. Although, these patients were diagnosed with mild asymptomatic CTRCD, careful long-term follow-up will be required.

Variation in the frozen lesion size according to the non-occluded application duration and technique for cryoballoon ablation.

OBJECTIVE: The frozen lesion formation created by cryoballoon ablation, especially with non-occluded applications, has not been fully evaluated. This study aimed to validate the lesion size under different cryoballoon ablation settings: application duration, push-up technique, and laminar flow. METHODS: The frozen lesion size was evaluated immediately after ending the freezing with three different application durations (120, 150, and 180 seconds) in porcine hearts (N = 24). During the application, the push-up technique was applied at 10, 20, and 30 seconds after starting the freezing with or without laminar flow. RESULTS: The lesion size was significantly correlated with the nadir balloon temperature (P<0.001). The lesion volume became significantly larger after 150 seconds than 120 seconds (1272mm3 versus 1709mm3, P = 0.004), but not after 150 seconds (versus 1876mm3 at 180 seconds, P = 0.29) with a comparable nadir balloon temperature. Furthermore, the lesion volume became significantly larger with the push-up technique with the largest lesion size with a 20-second push-up after the freezing (1193mm3 without the push-up technique versus 1585mm3 with a push-up at 10 seconds versus 1808mm3 with a push-up at 20 seconds versus 1714mm3 with a push-up at 30 seconds, P = 0.04). Further, the absence of laminar flow was not associated with larger lesion size despite a significantly lower nadir balloon temperature. CONCLUSION: The frozen lesion size created by cryoballoon ablation became larger with longer applications at least 150 seconds and with a push-up technique especially at 20 seconds after the freezing.

Effects of peripheral artery disease on long-term outcomes after percutaneous coronary intervention versus coronary artery bypass grafting in patients with severe coronary artery disease.

BACKGROUND: There is a scarcity of data evaluating the effect of peripheral artery disease (PAD) on long-term mortality after percutaneous coronary intervention (PCI) relative to coronary artery bypass grafting (CABG) in patients with severe coronary artery disease in real-world practice. METHODS: Among 14,867 consecutive patients who underwent their first coronary revascularization with PCI or isolated CABG between 2011 and 2013 in the CREDO-Kyoto PCI/CABG registry Cohort-3, the current study population consisted of 3380 patients with three-vessel coronary artery disease or left main coronary artery disease. Long-term clinical outcomes were compared between PCI and CABG stratified by the presence or absence of PAD. Median clinical follow-up was 5.9 (IQR: 5.1-6.8) years. RESULTS: There were 461 patients with PAD (PCI: N = 307, CABG: N = 154), and 2919 patients without PAD (PCI: N = 1823, CABG: N = 1096). The cumulative 5-year mortality after coronary revascularization was 31.2 % in patients with PAD and 16.2 % in those without PAD (p < 0.0001). There was a higher risk of PCI relative to CABG for all-cause death in patients with and without PAD (adjusted HR, 1.59; 95%CI, 0.99-2.53; p = 0.054, and HR, 1.25; 95%CI, 1.01-1.56; p = 0.04) without interaction (p interaction p = 0.48); Nevertheless, there was no excess risk of PCI relative to CABG for cardiovascular death regardless of PAD. CONCLUSIONS: The long-term mortality after coronary revascularization was significantly higher in severe CAD patients with PAD than those without PAD. There was a higher mortality risk of PCI relative to CABG in patients with and without PAD without interaction, which was mainly driven by excess non-cardiovascular deaths.

Impact of the Lumbar Arteries on Aneurysm Diameter and Type 2 Endoleak after Endovascular Aneurysm Repair.

BACKGROUND: Prophylactic embolization of the inferior mesenteric artery (IMA) during endovascular aneurysm repair (EVAR) is recommended to prevent type 2 endoleak (T2EL). However, the impact of patent lumbar arteries (LAs) on T2ELs and aneurysm diameter has not been elucidated. METHODS: Fifty-seven consecutive patients who underwent EVAR at our institution between January 2013 and September 2022 and whose IMA had been occluded preoperatively or newly occluded postoperatively were included in the study. Predictive factors for aneurysm sac enlargement, sac shrinkage, and T2EL were investigated. RESULTS: T2ELs occurred in 22.8% of the patients. The 4-year cumulative incidence rates of sac enlargement and shrinkage were 6.7% and 64.6%, respectively. The number of postoperative patent LAs was identified as a risk factor for T2ELs (95% confidence interval [CI]: 1.54-12.7, P = 0.0065). The number of postoperative patent LAs was found to be a significant predictor of sac enlargement (adjusted hazard ratio [AHR] 3.15, 95% CI: 1.43-6.96, P = 0.0045) and shrinkage (AHR 0.63, 95% CI: 0.43-0.91, P = 0.014). CONCLUSIONS: The current study demonstrated that the number of postoperative patent LAs had a significant impact on the development of T2ELs and the change in aneurysm diameter in patients in whom the IMA was occluded after EVAR.

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.

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.

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.

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.

Influence of low body weight on long-term clinical outcomes in patients with venous thromboembolism: From the COMMAND VTE registry.

INTRODUCTION: There is a paucity of data on the influence of low body weight on clinical outcomes in patients with acute venous thromboembolism (VTE). MATERIALS AND METHODS: The COMMAND VTE registry is a multicenter cohort study enrolling 3027 consecutive patients with acute symptomatic VTE. The current study population consisted of 2778 patients with available body weight value, who were divided into 2 groups; 1705 patients with lower body weight (≤60 kg) and 1073 patients with higher body weight (>60 kg). RESULTS: Patients with lower body weight were older (70.8 versus 60.9 years, P < 0.001), and more often women (75% versus 38%, P < 0.001), and more often had active cancer (27% versus 19%, P < 0.001) than those with higher body weight. The cumulative 5-year incidence of recurrent VTE was not significantly different between the 2 groups (10.6% versus 10.7%, P = 0.51). The cumulative 5-year incidences of major bleeding and all-cause death were significantly higher in patients with lower body weight than in those with higher body weight (14.6% versus 9.6%, P < 0.001, and 35.8% versus 19.8%, P < 0.001, respectively). The excess adjusted risk of patients with lower body weight relative to those with higher body weight remained significant for major bleeding and all-cause death (HR 1.57, 95%CI: 1.16-2.12, P = 0.003, and HR 1.50, 95%CI: 1.24-1.81, P < 0.001, respectively). CONCLUSIONS: In the current Japanese real-world registry, there were a high proportion of patients with low body weight, who had a higher risk for major bleeding and mortality without significant excess risk for recurrent VTE.

Periprocedural Stroke After Coronary Revascularization (from the CREDO-Kyoto PCI/CABG Registry Cohort-3).

There is a scarcity of data on incidence, risk factors, especially clinical severity, and long-term prognostic impact of periprocedural stroke after coronary revascularization in contemporary real-world practice. Among 14,867 consecutive patients undergoing first coronary revascularization between January 2011 and December 2013 (percutaneous coronary intervention [PCI]: N = 13258, and coronary artery bypass grafting [CABG]: N = 1609) in the Coronary Revascularization Demonstrating Outcome Study in Kyoto PCI/CABG registry Cohort-3, we evaluated the details on periprocedural stroke. Periprocedural stroke was defined as stroke within 30 days after the index procedure. Incidence of periprocedural stroke was 0.96% after PCI and 2.13% after CABG (log-rank p <0.001). Proportions of major stroke defined by modified Rankin Scale ≥2 at hospital discharge were 68% after PCI, and 77% after CABG. Independent risk factors of periprocedural stroke were acute coronary syndrome (ACS), carotid artery disease, advanced age, heart failure, and end-stage renal disease after PCI, whereas they were ACS, carotid artery disease, atrial fibrillation, chronic obstructive pulmonary disease, malignancy, and frailty after CABG. There was excess long-term mortality risk of patients with periprocedural stroke relative to those without after both PCI and CABG (hazard ratio 1.71 [1.25 to 2.33], and hazard ratio 4.55 [2.79 to 7.43]). In conclusion, incidence of periprocedural stroke was not negligible not only after CABG, but also after PCI in contemporary real-world practice. Majority of patients with periprocedural stroke had at least mild disability at hospital discharge. ACS and carotid artery disease were independent strong risk factors of periprocedural stroke after both PCI and CABG. Periprocedural stroke was associated with significant long-term mortality risk after both PCI and CABG.

Decline in Left Ventricular Ejection Fraction During Follow-Up in Patients With Severe Aortic Stenosis.

OBJECTIVES: The aim of this study was to investigate the prognostic impact of the decline in left ventricular ejection fraction (LVEF) at 1-year follow-up in patients with severe aortic stenosis (AS) managed conservatively. BACKGROUND: No previous study has explored the association between LVEF decline during follow-up and clinical outcomes in patients with severe AS. METHODS: Among 3,815 patients with severe AS enrolled in the multicenter CURRENT AS (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis) registry in Japan, 839 conservatively managed patients who underwent echocardiography at 1-year follow-up were analyzed. The primary outcome measure was a composite of AS-related deaths and hospitalization for heart failure. RESULTS: There were 91 patients (10.8%) with >10% declines in LVEF and 748 patients (89.2%) without declines. Left ventricular dimensions and the prevalence of valve regurgitation and atrial fibrillation or flutter significantly increased in the group with declines in LVEF. The cumulative 3-year incidence of the primary outcome measure was significantly higher in the group with declines in LVEF than in the group with no decline (39.5% vs. 26.5%; p < 0.001). After adjusting for confounders, the excess risk of decline in LVEF over no decline for the primary outcome measure remained significant (hazard ratio: 1.98; 95% confidence interval: 1.29 to 3.06). When stratified by LVEF at index echocardiography (≥70%, 60% to 69%, and <60%), the risk of decline in LVEF on the primary outcome was consistently seen in all the subgroups, without any interaction (p = 0.77). CONCLUSIONS: Patients with severe AS with >10% declines in LVEF at 1 year after diagnosis had worse AS-related clinical outcomes than those without declines in LVEF under conservative management. (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis Registry; UMIN000012140).

B-type natriuretic peptide in patients with asymptomatic severe aortic stenosis.

OBJECTIVES: We sought to evaluate the prognostic impact of the B-type natriuretic peptide (BNP) levels in patients with asymptomatic severe aortic stenosis (AS), who were not referred for aortic valve replacement (AVR). METHODS: We used data from a Japanese multicentre registry, the Contemporary outcomes after sURgery and medical tREatmeNT in patients with severe Aortic Stenosis Registry, which enrolled 3815 consecutive patients with severe AS. Of those, 387 asymptomatic patients who were not referred for AVR without left ventricular dysfunction and very severe AS were subdivided into four groups based on their BNP levels (BNP<100 pg/mL, n=201; 100≤BNP<200 pg/mL, n=94; 200≤BNP<300 pg/mL, n=42 and BNP>300 pg/mL, n=50). RESULTS: The cumulative 5-year incidence of AS-related events (aortic valve-related death or heart failure hospitalisation) was incrementally higher with increasing BNP level (14.2%, 29.6%, 46.3% and 47.0%, p<0.001). After adjusting for confounders, the risk for AS-related events was incrementally greater with increasing BNP levels (HR: 1.97, 95% CI: 0.97 to 3.98, p=0.06; HR: 3.59, 95% CI: 1.55 to 8.32, p=0.03 and HR: 7.38, 95% CI: 3.21 to 16.9, p<0.001, respectively). Notably, asymptomatic patients with BNPlevels of <100 pg/mL had an event rate of only 2.1% at 1 year. CONCLUSIONS: Increased BNP level was associated with a higher risk for AS-related adverse events in patients with asymptomatic severe AS with normal left ventricular ejection fraction who were not referred for AVR. Asymptomatic patients with BNP levels of <100 pg/mL had relatively low event rate, who might be safely followed with watchful waiting strategy. TRAIL REGISTRATION NUMBER: UMIN000012140.

Influence of a history of cancer on long-term cardiovascular outcomes after coronary stent implantation (an Observation from Coronary Revascularization Demonstrating Outcome Study-Kyoto Registry Cohort-2).

Aims: To evaluate the influence of a history of cancer on clinical outcomes in coronary artery disease (CAD) patients who underwent percutaneous coronary intervention (PCI). Methods and results: In the Coronary REvascularization Demonstrating Outcome Study in Kyoto (CREDO-Kyoto) PCI/coronary artery bypass grafting (CABG) Registry Cohort-2, there were 12 180 CAD patients who received PCI with stents. There were 1109 patients with a history of cancer (cancer group) and 11 071 patients without cancer (non-cancer group). The cumulative 5-year incidences of cardiac death and heart failure (HF) hospitalization were significantly higher in the cancer group than in the non-cancer group (12.4% vs. 7.5%, P < 0.001 and 12.1% vs. 7.6%, P < 0.001, respectively). Even after adjusting for confounders, the excess risk of the cancer group relative to non-cancer group for cardiac death and HF hospitalization remained significant [hazard ratio (HR) 1.27, 95% confidence interval (95% CI) 1.05-1.53; P = 0.02, and HR 1.39, 95% CI 1.13-1.68; P = 0.002, respectively]. Also, the cancer group had a trend toward higher adjusted risk for definite or probable stent thrombosis as compared with the non-cancer group (HR 1.49, 95% CI 0.99-2.16; P = 0.055). The cancer group had significantly higher adjusted risk for all-cause death, non-cardiac death, major bleeding, and non-CABG surgery than the non-cancer group, while the risks for myocardial infarction and stroke were neutral between the two groups. Conclusion: Patients with a history of cancer at the time of PCI had increased risk for cardiac events such as cardiac death and HF hospitalization as well as non-cardiac events such as non-cardiac death, major bleeding, and non-CABG surgery.

Malignant disease as a comorbidity in patients with severe aortic stenosis: clinical presentation, outcomes, and management.

Aim: To investigate the effect of malignancy on the outcomes of patients with severe aortic stenosis (AS) and the management strategy for AS with malignancy. Methods and results: Using data of 3815 patients with severe AS in a retrospective multicentre registry [CURRENT AS (Contemporary outcomes after sURgery and medical tREatmeNT in patients with severe Aortic Stenosis) registry], we compared 3-year clinical outcomes among three groups based on malignancy status: with malignancy currently under treatment including best supportive care (malignancy group), with a history of malignancy without any current treatment (past history group), or without history of malignancy (no malignancy group). Patients in the malignancy group (n = 124) were more often men and had higher prevalence of low body mass index, recurrence of malignancy, anaemia, and asymptomatic status, despite comparable surgical risks and echocardiographic parameters. The malignancy group or the past history group (n = 389) had significantly higher risk for all-cause death [hazard ratio (HR) 2.49, 95% CI (95% confidence interval) 1.98-3.14; HR 1.23, 95% CI 1.04-1.46] and for malignancy-related death (HR 16.2, 95% CI 10.64-24.54; HR 3.66, 95% CI 2.43-5.52) than that of the no malignancy group (n = 3302). The excess risk for aortic valve-related death was not observed in the malignancy group (HR 0.79, 95% CI 0.48-1.29) and was lower in the past history group (HR 0.72, 95% CI 0.53-0.96). In the malignancy group, the treatment strategy (surgery: n = 16, conservative management: n = 108) was determined based on the clinical status of AS or life expectancy. Conclusions: Malignancy had marked effect on all-cause death and malignancy-related death in patients with severe AS. History of malignancy also had a smaller but significant effect on mortality.

Prognostic Impact of Left Ventricular Ejection Fraction in Patients With Severe Aortic Stenosis.

OBJECTIVES: The aim of this study was to evaluate the prognostic impact of left ventricular ejection fraction (LVEF) in patients with severe aortic stenosis (AS). BACKGROUND: The prognostic impact of LVEF in severe AS remains controversial. METHODS: Among 3,815 consecutive patients with severe AS enrolled in the CURRENT AS (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis) registry, the present study population consisted of 3,794 patients after excluding 21 patients without LVEF data. Patients were divided into 4 groups according to LVEF at index echocardiography (<50%, 50% to 59%, 60% to 69%, and ≥70%; conservative strategy: n = 388, n = 390, n = 1,025, and n = 800; initial aortic valve replacement strategy: n = 206, n = 170, n = 375, and n = 440). Echocardiographic data were site reported, and there was no echocardiography core laboratory. RESULTS: In the conservative group, the cumulative 5-year incidence of the primary outcome measure (a composite of aortic valve-related death or heart failure hospitalization) was significantly higher in patients with LVEFs <50% and 50% to 59% than in those with LVEFs 60% to 69% and ≥70% (72.3%, 58.4%, 38.7%, and 35.0%, respectively, p < 0.001), whereas in the initial aortic valve replacement group, the negative effect of low LVEF was markedly attenuated (20.2%, 20.3%, 17.7%, and 12.4%, respectively, p = 0.03). After adjusting for confounders, LVEF <50% (hazard ratio: 1.82; 95% confidence interval: 1.44 to 2.28; p < 0.001) and 50% to 59% (hazard ratio: 1.77; 95% confidence interval: 1.42 to 2.20; p < 0.001) but not 60% to 69% (hazard ratio: 1.14; 95% confidence interval: 0.94 to 1.39; p = 0.17) were independently associated with poorer outcomes compared with LVEF ≥70% (reference) in the conservative group. In the initial aortic valve replacement group, the adjusted risk for the primary outcome measure was not significantly different across the 4 LVEF groups. CONCLUSIONS: This study demonstrates that survival in patients with severe AS is impaired when LVEF is <60%, and these findings have implications for decision making with regard to the timing of surgical intervention.

Second-Generation vs. First-Generation Drug-Eluting Stents in Patients With Calcified Coronary Lesions　- Pooled Analysis From the RESET and NEXT Trials.

BACKGROUND: The comparative efficacy of second-generation (G2) vs. first-generation (G1) drug-eluting stents (DES) for calcified coronary lesions is unknown.Methods and Results:We compared the 3-year clinical outcomes of patients with G1- or G2-DES according to the presence or absence of calcified coronary lesions as assessed in an angiographic core laboratory using data from 2 large-scale prospective multicenter randomized trials, RESET and NEXT. G1-DES and G2-DES were implanted in 299 and 1,033 patients, respectively, in the Calc stratum (≥1 lesion with moderate/severe calcification), and 1,208 and 3,550 patients, respectively, in the Non-calc stratum (no/mild calcification). The patients in the Calc stratum had a significantly higher adjusted risk for the primary outcome measure (any target-lesion revascularization (TLR)) than those in the Non-calc stratum (HR: 1.38, 95% CI: 1.11-1.71, P=0.004). The cumulative 3-year incidence of any TLR was not significantly different between the G1-DES and G2-DES groups in both the Calc and Non-calc strata (12.1% vs. 9.7%, P=0.22, and 6.8% vs. 6.1%, P=0.44, respectively). After adjusting for confounders, the effect of G2DES relative to G1-DES for any TLR remained insignificant in both the Calc and Non-calc strata (HR: 0.78, 95% CI: 0.48-1.25, P=0.3, and HR: 0.84, 95% CI: 0.61-1.17, P=0.31, respectively, P interaction=0.55). CONCLUSIONS: The effect of G2-DES relative to G1-DES for TLR was not significantly different regardless of the presence or absence of lesion calcification.

Causes of Death in Patients with Severe Aortic Stenosis: An Observational study.

Whether patients with severe aortic stenosis (AS) die because of AS-related causes is an important issue for the management of these patients. We used data from CURRENT AS registry, a Japanese multicenter registry, to assess the causes of death in severe AS patients and to identify the factors associated with non-cardiac mortality. We enrolled 3815 consecutive patients with a median follow-up of 1176 days; the 1449 overall deaths comprised 802 (55.3%) from cardiac and 647 (44.7%) from non-cardiac causes. Heart failure (HF) (25.7%) and sudden death (13.0%) caused the most cardiac deaths, whereas infection (13.0%) and malignancy (11.1%) were the main non-cardiac causes. According to treatment strategies, infection was the most common cause of non-cardiac death, followed by malignancy, in both the initial aortic valve replacement (AVR) cohort (N = 1197), and the conservative management cohort (N = 2618). Both non-cardiac factors (age, male, body mass index <22, diabetes, prior history of stroke, dialysis, anemia, and malignancy) and cardiac factors (atrial fibrillation, ejection fraction <68%, and the initial AVR strategy) were associated with non-cardiac death. These findings highlight the importance of close monitoring of non-cardiac comorbidities, as well as HF and sudden death, to improve the mortality rate of severe AS patients.

Prognostic Impact of Peak Aortic Jet Velocity in Conservatively Managed Patients With Severe Aortic Stenosis: An Observation From the CURRENT AS Registry.

BACKGROUND: There are limited data regarding the risk stratification based on peak aortic jet velocity (Vmax) in patients with severe aortic stenosis (AS). METHODS AND RESULTS: Among 3815 consecutive patients with severe AS enrolled in the CURRENT AS (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis) registry, the study population consisted of 1075 conservatively managed patients with Vmax ≥4.0 m/s and left ventricular ejection fraction ≥50%. The study patients were subdivided into 3 groups based on Vmax (group 1, 4.0 ≤ Vmax <4.5 m/s, N=550; group 2, 4.5 ≤ Vmax <5 m/s, N=279; and group 3, Vmax ≥5 m/s, N=246). Cumulative 5-year incidence of AS-related events (aortic valve-related death or heart failure hospitalization) was incrementally higher with increasing Vmax (entire population; 38.0%, 49.4%, and 62.8%, P<0.001; symptomatic patients; 55.7%, 60.9%, and 72.2%, P=0.008; and asymptomatic patients; 29.4%, 38.9%, and 47.7%, P=0.005). After adjusting for confounders, the excess risk of group 2 and group 3 relative to group 1 for AS-related events remained significant (hazard ratio, 1.39; 95% CI, 1.07-1.81; P=0.02, and hazard ratio, 1.53; 95% CI, 1.17-2.00; P=0.002, respectively). The effect size of group 3 relative to group 1 for AS-related events in asymptomatic patients (N=479) was similar to that in symptomatic patients (N=596; hazard ratio, 1.59; 95% CI, 1.01-2.52; P=0.047, and hazard ratio, 1.67; 95% CI, 1.16-2.40, P=0.008, respectively), and there was no significant overall interaction between the symptomatic status and the effect of the Vmax categories on AS-related events (interaction, P=0.88). CONCLUSIONS: In conservatively managed severe AS patients with preserved left ventricular ejection fraction, increasing Vmax was associated with incrementally higher risk for AS-related events. However, the cumulative 5-year incidence of the AS-related events remained very high even in asymptomatic patients with less greater Vmax.