Concomitant Mitral Regurgitation in Severe Aortic Stenosis　- Insights From the CURRENT AS Registry-2.

BACKGROUND: Data on concomitant mitral regurgitation (MR) in patients with severe aortic stenosis (AS) are scarce.Methods and Results: We investigated the risk of concomitant MR in patients with severe AS in the CURRENT AS Registry-2 according to initial treatment strategy (transcatheter aortic valve implantation [TAVI], surgical aortic valve replacement [SAVR], or conservative). Among 3,365 patients with severe AS, 384 (11.4%) had moderate/severe MR (TAVI: n=126/1,148; SAVR: n=68/591; conservative: n=190/1,626). The cumulative 3-year incidence for death or heart failure (HF) hospitalization was significantly higher in the moderate/severe than no/mild MR group in the entire population (54.6% vs. 34.3%, respectively; P<0.001) and for each treatment strategy (TAVI: 45.0% vs. 31.8% [P=0.006]; SAVR: 31.9% vs. 18.7% [P<0.001]; conservative: 67.8% vs. 41.6% [P<0.001]). The higher adjusted risk of moderate/severe MR relative to no/mild MR for death or HF hospitalization was not significant in the entire population (hazard ratio [HR] 1.15; 95% confidence interval [CI] 0.95-1.39; P=0.15); however, the risk was significant in the SAVR (HR 1.92; 95% CI 1.04-3.56; P=0.04) and conservative (HR 1.30; 95% CI 1.02-1.67; P=0.04) groups, but not in the TAVI group (HR 1.03; 95% CI 0.70-1.52; P=0.86), despite no significant interaction (Pinteraction=0.37). CONCLUSIONS: Moderate/severe MR was associated with a higher risk for death or HF hospitalization in the initial SAVR and conservative strategies, while the association was less pronounced in the initial TAVI strategy.

Clinically significant incidental noncardiac findings on preprocedural computed tomography in patients with aortic stenosis undergoing aortic-valve replacement.

BACKGROUND: There is a scarcity of data on the prevalence of abnormal findings on preprocedural computed tomography (CT) before aortic valve replacement (AVR) in patients with aortic stenosis (AS). METHODS: Among consecutive 593 patients with severe AS who were planned to undergo AVR, we evaluated the prevalence of clinically significant incidental noncardiac findings on preprocedural CT. Clinically significant incidental noncardiac findings were defined as newly detected abnormalities that required therapy, consultation for expert, further investigation, or clinical follow-up. RESULTS: The mean age was 82.0 years and 39.5 % of the patients were men. Of those, 78.4 % of the patients were treated with transcatheter aortic valve implantation (TAVI) and 21.6 % of the patients were treated with surgical AVR (SAVR). There were 271 clinically significant incidental noncardiac findings in 227 patients (38.3 %) including 2.5 % of malignancy. The prevalence of clinically significant incidental noncardiac findings were higher in the TAVI group than in the SAVR group (40.2 % versus 31.3 %). The prevalence of clinically significant incidental noncardiac findings were lower in patients under 60 years of age (10.0 %) than in patients over 60 years of age (60-69 years: 40.0 %, 70-79 years: 34.3 %, 80-89 years: 39.7 %, and ≥90 years: 42.1 %). CONCLUSIONS: Clinically significant incidental noncardiac findings were newly identified on preprocedural CT in approximately 40 % of patients with severe AS undergoing AVR including 2.5 % of malignancy.

Impact of changes in Achilles tendon thickening on cardiovascular events in patients with familial hypercholesterolemia.

Background: Achilles tendon thickening (ATT) can be ameliorated by lowering low-density lipoprotein (LDL) levels in patients with familial hypercholesterolemia (FH). The Japan Atherosclerosis Society (JAS) defines ATT as ≥8.0 mm in males and ≥7.5 mm in females. We aimed to determine the clinical impact of changes in ATT on the development of major adverse cardiovascular events (MACE). Methods: Patients with clinically diagnosed heterozygous FH (HeFH) (N = 1273; 614 males, 659 females) with ATT data from X-ray were assessed. Patients were divided into four groups: patients without ATT from baseline until follow-up (group 1), patients without ATT at baseline but developed ATT at follow-up (group 2), patients with ATT at baseline but regressed at follow-up (group 3), and patients with ATT from baseline until follow-up (group 4). Cox proportional hazard models were used to assess the factors associated with MACE, including cardiovascular death and any coronary events. Results: On follow-up (median: 10.9 years), 142 MACEs were observed, and the median ATT regressed from 7.8 to 7.6 mm. Changes in ATT were significantly associated with the occurrence of MACE in all groups, when compared to group 1 (hazard ratio [HR]: 2.73; 95 % confidence interval [CI]: 1.33-4.13 [p < 0.001], HR: 2.18, 95 % CI: 1.08-3.28, [p < 0.001], HR: 6.34, 95 % CI: 3.10-9.58, [p < 0.001], in groups 2, 3, and 4, respectively). Conclusions: Assessing ATT has diagnostic value and allows for risk stratification among patients with HeFH.

Association between remnant cholesterol and incident atherosclerotic cardiovascular disease, heart failure, and atrial fibrillation.

BACKGROUND: It remains unclear if remnant cholesterol is associated with atherosclerotic cardiovascular disease (ASCVD) (myocardial infarction, angina pectoris and stroke), heart failure (HF), and atrial fibrillation (AF) under primary prevention settings. OBJECTIVE: We aimed to clarify this issue among a general population without a history of ASCVD, HF or AF. METHODS: Analyses were conducted with a nationwide health claims database collected in the JMDC Claims Database between 2005 and 2022 (n = 1,313,722; median age, 42 years; 54.6% men). We assessed the associations between remnant cholesterol calculated as total cholesterol minus HDL cholesterol minus LDL cholesterol and composite CVD outcomes, including, ASCVD, HF, and AF using Cox proportional hazard model, dividing the individuals into tertiles of remnant cholesterol (T1-T3). RESULTS: The mean follow-up duration was 3.0 years. In total, 43,755 events were recorded. Remnant cholesterol was significantly associated with composite CVD outcomes after adjustments (T3 vs T1: hazard ratio [HR]; 1.07, 95% confidence interval [CI]: 1.04-1.10, p-trend<0.001). Remnant cholesterol was associated with myocardial infarction (T3 vs T1:HR: 1.20, 95% CI: 1.06-1.34, p-trend=0.002), angina pectoris (T3 vs T1:HR: 1.09, 95% CI: 1.05-1.14, p-trend<0.001), stroke (T3 vs T1:HR: 1.08, 95% CI: 1.02-1.14, p-trend=0.007), and HF (T3 vs T1:HR: 1.08, 95% CI: 1.04-1.12, p-trend<0.001), while we found a marginal inverse association between remnant cholesterol and AF (T3 vs T1:HR: 0.92, 95% CI: 0.86-1.00, p-trend=0.054). CONCLUSION: Remnant cholesterol was positively associated with ASCVD and HF, while we found a marginal inverse association between remnant cholesterol and AF.

In-hospital outcomes after SAVR or TAVI in patients with severe aortic stenosis.

There were no data comparing the in-hospital outcomes after transcatheter aortic valve implantation (TAVI) with those after surgical aortic valve replacement (SAVR) in Japan. Among consecutive patients with severe AS between April 2018 and December 2020 in the CURRENT AS Registry-2, we identified 1714 patients who underwent aortic valve replacement (TAVI group: 1134 patients, and SAVR group: 580 patients). Patients in the TAVI group were much older (84.4 versus 73.6 years, P < 0.001) and more often had comorbidities than those in the SAVR group. In-hospital death rate was numerically lower in the TAVI group than in the SAVR group (0.6% versus 2.2%). After excluding patients with dialysis, in-hospital death rate was very low and comparable in the TAVI and SAVR groups (0.6% versus 0.8%). The rates of major bleeding and new-onset atrial fibrillation during index hospitalization were higher after SAVR than after TAVI (72% versus 20%, and 26% versus 4.6%, respectively), while the rate of pacemaker implantation was higher after TAVI than after SAVR (8.1% versus 2.4%). Regarding the echocardiographic data at discharge, the prevalence of patient-prosthesis mismatch was lower in the TAVI group than in the SAVR group (moderate: 9.0% versus 26%, and severe: 2.6% versus 4.8%). In this real-world data in Japan, TAVI compared with SAVR was chosen in much older patients with more comorbidities with severe AS. In-hospital death rate was numerically lower in the TAVI group than in the SAVR group.

Familial hypercholesterolemia is related to cardiovascular disease, heart failure and atrial fibrillation. Results from a population-based study.

BACKGROUND: Familial hypercholesterolemia (FH) is associated with atherosclerotic cardiovascular disease (ASCVD). However, the prevalence of FH among a general population remains unknown, and it is unclear if FH is associated with other cardiovascular complications, including heart failure (HF) and atrial fibrillation (AF). METHODS: Analyses were conducted on individuals without a prior history of cardiovascular disease using a nationwide health claims database collected in the JMDC Claims Database between 2005 and 2022 (n = 4,126,642; median age, 44 years; 57.5% men). We defined FH as either LDL cholesterol ≥250 mg/dL or LDL cholesterol ≥175 mg/dL under the lipid-lowering medications under the assumption that lipid-lowering medications reduced LDL cholesterol by 30%. We assessed the associations between FH and composite outcomes, including, ASCVD (myocardial infarction, angina pectoris, and stroke), HF, and AF using Cox proportional hazard model. RESULTS: We identified 11,983 (.29%) FH patients. In total, 181,150 events were recorded during the mean follow-up period of 3.5 years. The status FH was significantly associated with composite outcomes after adjustments (hazard ratio [HR]; 1.38, 95% confidence interval [CI]: 1.30-1.47, p < .001). Interestingly, the status FH was significantly associated with HF (HR: 1.48, 95% CI: 1.36-1.61, p < .001) and AF (HR: 1.33, 95% CI: 1.08-1.64, p < .001) in addition to angina pectoris (HR: 1.45, 95% CI: 1.33-1.58, p < .001) and stroke (HR: 1.19, 95% CI: 1.04-1.36, p < .001). CONCLUSION: We found that the prevalence of FH was .29% in a general population. FH was significantly associated with a higher risk of developing cardiovascular disease, HF and AF. LAY SUMMARY: We sought to identify the prevalence of FH among a general population, and to clarify whether FH increases the risk of not only ASCVD but also HF and AF.

Clinical Characteristics of Homozygous Familial Hypercholesterolemia in Japan: A Survey Using a National Database.

Background: The studies evaluating patients' characteristics and lipid-lowering therapy for patients with homozygous familial hypercholesterolemia (HoFH) are scarce. Objectives: This study aims to evaluate the characteristics of and treatments for patients with HoFH. Methods: This study included 201 patients who were diagnosed with definite or probable HoFH from the National Database of the Japanese Ministry of Health, Labour, and Welfare. Results: The patients' median age at diagnosis was 27 years and exhibited a bimodal distribution. Approximately 70% of patients had coronary artery disease. Regarding genetic backgrounds, mutations in the low-density lipoprotein (LDL) receptor (LDLR) were identified in most of the patients, followed by proprotein convertase subtilisin/kexin type 9 (PCSK9) and double heterozygotes of LDLR. High-intensity statins were introduced to 74% of the patients, lipoprotein apheresis was performed in 21%, and PCSK9 inhibitors were administered to 50%. The mean of LDL cholesterol before and after treatment were 10.1 mmol/L and 3.9 mmol/L, respectively. Patients with coronary artery disease had significantly decreased LDL cholesterol. A quarter of the patients (n = 49, 24%) exhibited valvular diseases, particularly aortic valvular disease (n = 34, 61%). Conclusions: The national epidemiological study of patients with HoFH showed patient's clinical and genetic characteristics and LDL-lowering therapy in Japan. There was considerable diversity in the severity of phenotypes, including LDL cholesterol levels, among patients with HoFH. In Japan, the management of LDL cholesterol in HoFH is still inadequate despite the availability of intensive lipid-lowering therapies.

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.

The Impact of Mitral Regurgitation on Long-Term Outcomes in Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention.

It is important to clarify the precise impact of mitral regurgitation (MR) on long-term outcomes in acute myocardial infarction (AMI) patients who underwent percutaneous coronary intervention (PCI). In the Coronary Revascularization Demonstrating Outcome study in Kyoto Acute Myocardial Infarction (CREDO-Kyoto AMI) Registry Wave-2, the study population consisted of 5,266 patients with AMI who underwent PCI. The clinical outcomes of all-cause death, cardiovascular death, and hospitalization for heart failure (HF) were compared according to the severity of MR. Mild and moderate/severe MR were identified in 2,112 (40%) and 531 patients (10%), respectively. Patients with greater severity of MR were more likely to be old, had more co-morbidities, and more often presented with large myocardial infarction with HF. During median follow-up duration of 5.6 (interquartile range: 4.2 to 6.6) years, as the MR severity increased from no, mild, to moderate/severe MR, the cumulative 5-year incidences of all-cause death, cardiovascular death and hospitalization for HF incrementally increased ([15.3%, 19.6%, 33.3%], [8.9%, 11.7%, 21.0%] and [5.9%, 12.4%, 23.9%], respectively, P for all<0.001). After adjusting for confounders, however, mild and moderate/severe MR were not independently associated with the higher risks for all-cause death (hazard ratio [95% confidence interval]:1.05 [0.92 to 1.19], p = 0.51, and 1.10 [0.92 to 1.32], p = 0.28) and cardiovascular death (1.01 [0.85 to 1.21], p = 0.89, and 0.93 [0.73 to 1.18], p = 0.54) as compared with no MR. Both mild and moderate/severe MR were independently associated with the higher risks for hospitalization for HF (1.73 [1.42 to 2.11], p <0.001, and 2.23 [1.73 to 2.87], p <0.001). In a large population of patients with AMI who underwent PCI, MR was not independently associated with higher long-term mortality risk but was independently associated with higher risk for hospitalization for HF.

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.

Modifiers of the Risk of Diabetes for Long-Term Outcomes After Coronary Revascularization: CREDO-Kyoto PCI/CABG Registry.

Background: Diabetes is a well-known risk factor for adverse outcomes after coronary revascularization. Objectives: This study sought to determine high-risk subgroups in whom the excess risks of diabetes relative to nondiabetes are particularly prominent and thus may benefit from more aggressive interventions. Methods: The study population consisted of 39,427 patients (diabetes: n = 15,561; nondiabetes: n = 23,866) who underwent first percutaneous coronary intervention (n = 33,144) or coronary artery bypass graft (n = 6,283) in the pooled CREDO-Kyoto PCI/CABG (Coronary Revascularization Demonstrating Outcome Study in Kyoto Percutaneous Coronary Intervention/Coronary Artery Bypass Graft) registry. The primary outcome measure was major adverse cardiovascular and cerebral endpoints (MACCE), which was defined as a composite of all-cause death, myocardial infarction, and stroke. Results: With median follow-up of 5.6 years, diabetes was associated with significantly higher adjusted risks for MACCE. The excess adjusted risks of diabetes relative to nondiabetes for MACCE increased with younger age (≤64 years: adjusted HR: 1.30; 95% CI: 1.19-1.41; P < 0.001; 64-73 years: adjusted HR: 1.24; 95% CI: 1.16-1.33; P < 0.001; >73 years: adjusted HR: 1.17; 95% CI: 1.10-1.23; P < 0.001; P interaction < 0.001), mainly driven by greater excess adjusted mortality risk of diabetes relative to nondiabetes in younger tertile. No significant interaction was observed between adjusted risk of diabetes relative to nondiabetes for MACCE and other subgroups such as sex, mode of revascularization, and clinical presentation of acute myocardial infarction. Conclusions: The excess risk of diabetes relative to nondiabetes for MACCE was profound in the younger population. This observation suggests more aggressive interventions for secondary prevention in patients with diabetes might be particularly relevant in younger patients.

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.

Stroke Risk Stratification With the CHADS2 Score in Patients Without Atrial Fibrillation Who Underwent Percutaneous Coronary Intervention.

The clinical significance of the CHADS2 score remains unclear in patients with coronary artery disease (CAD) without atrial fibrillation (AF). Therefore, the purpose of this study was to evaluate the association between the CHADS2 score and the long-term risk of ischemic stroke and its severity in patients with CAD with and without AF. Using the CREDO (Coronary Revascularization Demonstrating Outcome study)-Kyoto Registry Cohort-3, the present study population consisted of 11,516 patients with CAD who underwent percutaneous coronary intervention without oral anticoagulants at discharge. We divided the patients into 2 groups according to the presence (n = 721) or absence (n = 10,795) of AF. As the CHADS2 score increased from 0 or 1 to 6, the cumulative 5-year incidence of ischemic stroke incrementally increased from 2.1% to 17.1% in patients without AF and from 4.2% to 40.7% in patients with AF. The cumulative 5-year incidence of ischemic stroke in patients without AF and a CHADS2 score of 2 were numerically comparable to that in patients with AF and a CHADS2 score of 1 (3.4% and 3.7%). In the 423 patients who developed ischemic stroke, the modified Rankin Scale score was not significantly different between patients with and without AF (p for trend = 0.12). In patients with and without AF, the increase in the CHADS2 score was significantly associated with the greater prevalence of higher modified Rankin Scale scores (p for trend = 0.03 and <0.001, respectively). An increasing CHADS2 score was associated with an incrementally increased risk for ischemic stroke and greater severity of ischemic stroke in patients with and without AF.

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.

Differences in mortality and causes of death between STEMI and NSTEMI in the early and late phases after acute myocardial infarction.

BACKGROUND: The detailed causes of death in non-ST-segment-elevation myocardial infarction (NSTEMI) have not been adequately evaluated compared to those in ST-segment elevation myocardial infarction (STEMI). METHODS: The study population was 6,228 AMI patients who underwent percutaneous coronary intervention (STEMI: 4,625 patients and NSTEMI: 1,603 patients). The primary outcome was all-cause death. RESULTS: Within 6 months after AMI, the adjusted mortality risk was not significantly different between NSTEMI patients and STEMI patients (HR: 0.83, 95%CI: 0.67-1.03, P = 0.09). Regarding the causes of death within 6 months after AMI, mechanical complications more frequently occurred in STEMI patients than in NSTEMI patients, while proportions of post resuscitation status on arrival and heart failure were higher in in NSTEMI patients than in STEMI patients. Beyond 6 months after AMI, the adjusted mortality risk of NSTEMI relative to STEMI was not significantly different. (HR: 1.04, 95%CI: 0.90-1.20, P = 0.59). Regarding causes of death beyond 6 months after AMI, almost half of deaths were cardiovascular causes in both groups, and breakdown of causes of death was similar between NSTEMI and STEMI. CONCLUSION: The mortality risk within and beyond 6 months after AMI were not significantly different between STEMI patients and NSTEMI patients after adjusting confounders. Deaths due to post resuscitation status and heart failure were more frequent in NSTEMI within 6 months after AMI.

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.

Newly Diagnosed Atrial Fibrillation in Acute Myocardial Infarction.

Background It remains controversial whether long-term clinical impact of newly diagnosed atrial fibrillation (AF) in the acute phase of acute myocardial infarction (AMI) is different from that of prior AF diagnosed before the onset of AMI. Methods and Results The current study population from the CREDO-Kyoto AMI (Coronary Revascularization Demonstrating Outcome Study in Kyoto Acute Myocardial Infarction) Registry Wave-2 consisted of 6228 patients with AMI who underwent percutaneous coronary intervention. The baseline characteristics and long-term clinical outcomes were compared according to AF status (newly diagnosed AF: N=489 [7.9%], prior AF: N=589 [9.5%], and no AF: N=5150 [82.7%]). Median follow-up duration was 5.5 years. Patients with newly diagnosed AF and prior AF had similar baseline characteristics with higher risk profile than those with no AF including older age and more comorbidities. The cumulative 5-year incidence of all-cause death was higher in newly diagnosed AF and prior AF than no AF (38.8%, 40.7%, and 18.7%, P<0.001). The adjusted hazard ratios (HRs) for mortality of newly diagnosed AF and prior AF relative to no AF remained significant with similar magnitude (HR, 1.31; 95% CI, 1.12-1.54; P<0.001, and HR, 1.32; 95% CI, 1.14-1.52; P<0.001, respectively). The cumulative 5-year incidence of stroke decreased in the order of newly diagnosed AF, prior AF and no AF (15.5%, 12.9%, and 6.3%, respectively, P<0.001). The higher adjusted HRs of both newly diagnosed AF and prior AF relative to no AF were significant for stroke, with a greater risk of newly diagnosed AF than that of prior AF (HR, 2.05; 95% CI, 1.56-2.69; P<0.001, and HR, 1.33; 95% CI, 1.00-1.78; P=0.048, respectively). The higher stroke risk of newly diagnosed AF compared with prior AF was largely driven by the greater risk within 30 days. The higher adjusted HRs of newly diagnosed AF and prior AF relative to no AF were significant for heart failure hospitalization (HR, 1.73; 95% CI, 1.35-2.22; P<0.001, and HR, 2.23; 95% CI, 1.82-2.74; P<0.001, respectively) and major bleeding (HR, 1.46; 95% CI, 1.23-1.73; P<0.001, and HR, 1.36; 95% CI, 1.15-1.60; P<0.001, respectively). Conclusions Newly diagnosed AF in AMI had risks for mortality, heart failure hospitalization, and major bleeding higher than no AF, and comparable to prior AF. The risk of newly diagnosed AF for stroke might be higher than that of prior AF.