Prognostic Value of Cardiovascular Biomarkers in the Population.

Importance: Identification of individuals at high risk for atherosclerotic cardiovascular disease within the population is important to inform primary prevention strategies. Objective: To evaluate the prognostic value of routinely available cardiovascular biomarkers when added to established risk factors. Design, Setting, and Participants: Individual-level analysis including data on cardiovascular biomarkers from 28 general population-based cohorts from 12 countries and 4 continents with assessments by participant age. The median follow-up was 11.8 years. Exposure: Measurement of high-sensitivity cardiac troponin I, high-sensitivity cardiac troponin T, N-terminal pro-B-type natriuretic peptide, B-type natriuretic peptide, or high-sensitivity C-reactive protein. Main Outcomes and Measures: The primary outcome was incident atherosclerotic cardiovascular disease, which included all fatal and nonfatal events. The secondary outcomes were all-cause mortality, heart failure, ischemic stroke, and myocardial infarction. Subdistribution hazard ratios (HRs) for the association of biomarkers and outcomes were calculated after adjustment for established risk factors. The additional predictive value of the biomarkers was assessed using the C statistic and reclassification analyses. Results: The analyses included 164 054 individuals (median age, 53.1 years [IQR, 42.7-62.9 years] and 52.4% were women). There were 17 211 incident atherosclerotic cardiovascular disease events. All biomarkers were significantly associated with incident atherosclerotic cardiovascular disease (subdistribution HR per 1-SD change, 1.13 [95% CI, 1.11-1.16] for high-sensitivity cardiac troponin I; 1.18 [95% CI, 1.12-1.23] for high-sensitivity cardiac troponin T; 1.21 [95% CI, 1.18-1.24] for N-terminal pro-B-type natriuretic peptide; 1.14 [95% CI, 1.08-1.22] for B-type natriuretic peptide; and 1.14 [95% CI, 1.12-1.16] for high-sensitivity C-reactive protein) and all secondary outcomes. The addition of each single biomarker to a model that included established risk factors improved the C statistic. For 10-year incident atherosclerotic cardiovascular disease in younger people (aged <65 years), the combination of high-sensitivity cardiac troponin I, N-terminal pro-B-type natriuretic peptide, and high-sensitivity C-reactive protein resulted in a C statistic improvement from 0.812 (95% CI, 0.8021-0.8208) to 0.8194 (95% CI, 0.8089-0.8277). The combination of these biomarkers also improved reclassification compared with the conventional model. Improvements in risk prediction were most pronounced for the secondary outcomes of heart failure and all-cause mortality. The incremental value of biomarkers was greater in people aged 65 years or older vs younger people. Conclusions and Relevance: Cardiovascular biomarkers were strongly associated with fatal and nonfatal cardiovascular events and mortality. The addition of biomarkers to established risk factors led to only a small improvement in risk prediction metrics for atherosclerotic cardiovascular disease, but was more favorable for heart failure and mortality.

Left atrial strain time integral evaluated by two-dimensional speckle tracking predicts left atrial appendage dysfunction in patients with acute ischemic stroke.

Cardioembolic stroke is a serious disease with poor prognosis, whose main embolic source is the left atrial appendage (LAA). Left atrial (LA) strain evaluated by the two-dimensional (2D) speckle tracking technique has been proposed. However, the commonly used peak LA strain reflects only LA reservoir function. The LA strain also includes indicators of the other LA functions, such as booster pump function, which reflects active contraction of the LA. This study aimed to investigate whether a newly developed parameter, the left atrial strain time integral (LASTI), can evaluate LAA dysfunction more accurately in patients with acute stroke. We measured LA strain using a 2D speckle tracking method in 168 patients with acute stroke and 20 age-matched control subjects. LASTI was calculated as the area under the LA strain curve in one cardiac cycle. LAA dysfunction was defined as LAA thrombus and/or severe spontaneous echo contrast by transesophageal echocardiography. LASTI was significantly lower in patients with LAA dysfunction than those without. LASTI was a better correlation with LAA blood flow velocity measured by transesophageal echocardiography than peak LA strain. Multivariate logistic regression analysis showed that LASTI was an independent predictor of LAA dysfunction after adjustment for conventional risk factors. LASTI can be a feasible parameter for predicting LAA dysfunction in patients with acute stroke.

Growth Differentiation Factor-15 and Clinical Outcomes in Lower Extremity Artery Disease.

AIM: Lower extremity artery disease (LEAD) is an increasingly common health problem that is associated with high mortality due to thrombotic and bleeding events. Growth differentiation factor-15 (GDF15), a stress-response cytokine belonging to the transforming growth factor-beta superfamily, is associated with cardiovascular disease and its outcomes. The aim of the present study was to examine the effect of serum GDF15 levels on clinical outcomes in patients with LEAD. METHODS: We measured serum GDF15 levels in 200 patients with LEAD before their initial endovascular therapy. The primary endpoint was the all-cause mortality rate. The secondary endpoints, on the other hand, were thrombotic and bleeding events, such as cerebral infarction, acute coronary syndrome, acute limb ischemia, and Bleeding Academic Research Consortium types 3 and 5. RESULTS: The serum GDF15 levels increased with advancing Fontaine class. Kaplan-Meier analysis revealed that the high-GDF15 group (≥ 2,275 pg/mL) had higher rates of all-cause deaths and thrombotic and bleeding events than the low-GDF15 group (＜2,275 pg/mL). Multivariate Cox proportional-hazards regression analysis revealed that GDF15 was an independent predictor of all-cause mortality and thrombotic and bleeding events after adjusting for confounding risk factors. When the ABC-AF-bleeding score was substituted for GDF15, similar results were obtained. CONCLUSION: Serum GDF15 levels were associated with all-cause mortality and thrombotic and bleeding events in patients with LEAD. Serum GDF15 is a potentially useful marker of clinical outcomes, specifically for tracking thrombotic and bleeding events in patients with LEAD.

Participant Selection from the General Japanese Population for Pulmonary Function Tests Using a Questionnaire on Symptoms and Smoking Habits during Annual Health Checkups: The Yamagata-Takahata Study.

Objective Pulmonary function tests are essential for diagnosing respiratory diseases, such as chronic obstructive pulmonary disease (COPD), but are typically not performed in Japan during annual health checkups, which hinders the early diagnosis of respiratory diseases. Methods Individuals who agreed to participate in the Yamagata-Takahata study during medical checkups in Takahata (Yamagata Prefecture, Japan) in 2011 were examined. We interviewed 669 participants (49.0% men; mean age, 67.7 years old) regarding their respiratory symptoms and smoking habits and performed pulmonary function tests during the study. Results Based on pulmonary function test results, 141 participants had pulmonary dysfunction, and 115 had obstructive pulmonary dysfunction. The risk of respiratory dysfunction, particularly obstructive respiratory dysfunction, was examined by referring to a questionnaire tool for an early COPD diagnosis. The associations between age, the smoking history, respiratory symptoms, and obstructive respiratory dysfunction were evaluated. Obstructive respiratory dysfunction was found in 17.6% of participants ≥50 years old and 19.5% ≥60 years old, 30.3% had a smoking history, and 32.8% had respiratory symptoms. Furthermore, the participants with multiple factors had a higher probability of obstructive respiratory dysfunction. Conclusion Subjects with obstructive pulmonary dysfunction are expected to be efficiently identified by extracting individuals by age and smoking habit and through a respiratory symptom questionnaire, although pulmonary function tests cannot be performed for all individuals during health checkups.

Hypokalemia, Kidney Function, and Clinical Outcomes in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is an increasing health problem associated with high morbidity and mortality rates. Several reports have shown an association between hypokalemia and clinical outcomes in patients with heart failure (HF). However, the association of hypokalemia with kidney function and clinical outcomes in patients with HFpEF remains unclear.Methods and Results: We measured serum potassium levels and kidney function in 454 patients with HFpEF (mean age 76 years; 55% men) at admission. Hypokalemia (K+<3.5 mmol/L) and hyperkalemia (K+>5.0 mmol/L) were identified in 58 (12.7%) and 11 (2.4%) patients, respectively. Patients with hypokalemia showed renal tubular damage (RTD), defined as a urinary ß2-microglobulin to creatinine ratio ≥300 µg/gCr, preserved estimated glomerular filtration rate (eGFR), and plasma volume expansion. Multivariate logistic analysis demonstrated that RTD, preserved eGFR, and plasma volume expansion were significantly associated with hypokalemia. During the median follow-up period of 1,000 days, 82 HF-related events occurred. Kaplan-Meier analysis showed that patients with hypokalemia had a higher rate of HF-related events than those without hypokalemia. Multivariate Cox proportional hazard regression analysis demonstrated that hypokalemia was significantly associated with HF-related events after adjusting for confounding factors. CONCLUSIONS: Hypokalemia is affected by kidney function, notably RTD, in patients with HFpEF. Hypokalemia is a risk factor for HF-related events in patients with HFpEF.

Anticoagulation therapy for endocardial/epicardial ablation of infarct-related ventricular tachycardia in a patient with antithrombin deficiency.

In patients with a history of antithrombin deficiency, a direct thrombin inhibitor may be considered as an alternative to intraprocedural anticoagulation. A 55-year-old woman with antithrombin deficiency and prior myocardial infarction suffered from electrical storm and appropriate defibrillator shocks. Substrate mapping guided left ventricular endocardial and epicardial ablations were successfully performed. The direct thrombin inhibitor, argatroban, was safely used as intraprocedural anticoagulation therapy with no complications. Learning objective: Optimal anticoagulation during endocardial and epicardial catheter ablation is essential to prevent thromboembolic and bleeding complications. Although patients with infarct-related electrical storm and antithrombin deficiency require unusual attention to anticoagulation, argatroban, a direct thrombin inhibitor, was safely used as intraprocedural anticoagulation therapy during catheter ablations, with no complications.

A case of a transcatheter valve-in-valve implantation using balloon expandable valve for failed SOLO SMART stentless bioprosthetic valve.

A 74-year-old man who had undergone surgical aortic valve replacement with the SOLO SMART stentless bioprosthetic valve 25 mm (LivaNova PLC, London, UK) and mitral valve replacement with MOSAIC 29 mm (Medtronic, Minneapolis, USA) 4 years previously was diagnosed with congestive heart failure, and transferred to our hospital. Echocardiography revealed severe aortic regurgitation caused by degraded bioprosthetic valve. He required continuous dobutamine administration to maintain hemodynamics. As a result of heart team discussion, we decided to perform transcatheter valve-in-valve implantation (ViV-TAVI) using balloon expandable valve (Sapien 3, Edwards Lifesciences, Irvine, USA). Since SOLO SMART stentless valve was placed to Valsalva sinus at the supra-annular level with continuous sutures, we planned to anchor TAVI valve 4 mm to the left ventricular side from the bottom of the failed stentless valve. Two pigtail catheters were placed at the bottom of the failed stentless valve leaflet to mark the nadir of stentless valve. After ViV-TAVI, the patient no longer required catecholamine administration and was discharged home one month later. This is the first case of ViV-TAVI using balloon expandable valve for failed SOLO SMART stentless bioprosthetic valve in a Japanese patient. Learning objective: Transcatheter valve-in-valve implantation (ViV-TAVI) for stentless valves is known to be technically challenging due to poor fluoroscopic visibility. Because the SOLO SMART stentless bioprosthetic valve is sutured to the wall of the sinus of Valsalva above the annulus, the landing point of transcatheter heart valve is at a native annulus which is lower than the bottom of the SOLO SMART leaflet. We describe the first Japanese case of ViV-TAVI with balloon expandable valve for the SOLO SMART stentless bioprosthetic valve.

Percutaneous coronary intervention for ST-elevation myocardial infarction complicated by cardiogenic shock in a super-aging society.

AIMS: ST-segment elevation myocardial infarction complicated by cardiogenic shock (STEMICS) is associated with substantial mortality. As life expectancy increases, percutaneous coronary intervention (PCI) is being performed more frequently, even in elderly patients with acute myocardial infarction (AMI). This study sought to investigate the characteristics and impact of PCI on in-hospital mortality in patients with STEMICS. METHODS AND RESULTS: The Japan AMI Registry (JAMIR) is a retrospective, nationwide, real-world database. Among 46 242 patients with AMI hospitalized in 2011-2016, 2760 patients with STEMICS (median age, 72 years) were studied. We compared 2396 (86.8%) patients who underwent PCI with 364 (13.2%) patients who did not. The percentage of mechanical circulatory support use in patients with STEMICS was 69.3% and in-hospital mortality was 34.6%. Compared with patients who did not undergo PCI, patients undergoing PCI were younger and had a higher rate of intra-aortic balloon pump use. A higher proportion was male or current smokers. In-hospital mortality was significantly lower in the PCI group than in the no-PCI group (31.3% vs. 56.0%, P < 0.001). Percutaneous coronary intervention was independently associated with lower in-hospital mortality [adjusted odds ratio (OR), 0.508; 95% confidence interval (CI), 0.347-0.744]. In 789 (28.6%) patients aged ≥80 years, PCI was associated with fewer in-hospital cardiac deaths (adjusted OR, 0.524; 95% CI, 0.281-0.975), but was not associated with in-hospital mortality (adjusted OR, 0.564; 95% CI, 0.300-1.050). CONCLUSION: In Japan, PCI was effective in reducing in-hospital cardiac death in elderly patients with STEMICS. Age alone should not preclude potentially beneficial invasive therapy.

Improved cerebral blood flow and hippocampal blood flow in stroke-free patients after catheter ablation of atrial fibrillation.

INTRODUCTION: Atrial fibrillation (AF) is a risk factor for reduced cerebral blood flow (CBF) and cognitive dysfunction, even in stroke-free patients. We aimed to test the hypothesis that CBF and hippocampal blood flow (HBF), measured with arterial spin labeling magnetic resonance imaging (MRI), improve after catheter ablation of AF to achieve sinus rhythm (SR). METHODS: A total of 84 stroke-free patients (63.1 ± 9.1 years; paroxysmal AF, n = 50; non-paroxysmal AF, n = 34) undergoing AF catheter ablation were included. MRI studies were done before, 3 months, and 12 months after the procedure with CBF and HBF measurements. RESULTS: Baseline CBF and HBF values in 50 paroxysmal AF patients were used as controls. Baseline CBF was higher in patients with paroxysmal AF than with non-paroxysmal AF (100 ± 32% vs. 86 ± 28%, p = .04). Patients with non-paroxysmal AF had increased CBF 3 months after AF ablation (86 ± 28% to 99 ± 34%, p = .03). Differences in CBF and HBF were greater in the group with AF restored to SR (p < .01). Both CBF and HBF levels at 12 months were unchanged from the 3 months level. Successful rhythm control by catheter ablation was an independent predictor of an increase in CBF > 17.5%. The Mini-Mental State Examination score improved after ablation (p = .02). CONCLUSION: SR restoration with catheter ablation was associated with improved CBF and HBF at 3 months, maintenance of blood flow, and improved cognitive function at 12 months.

Amiodarone-induced syndrome of inappropriate antidiuresis with hepatic transaminitis.

A 72-year-old woman with hypertrophic cardiomyopathy was admitted to the hospital after an appropriate implantable cardioverter-defibrillator shock for ventricular fibrillation. She was discharged after the addition of amiodarone. Eight months after discharge, she was admitted to the hospital with a sign of somnolence. She had low levels of serum sodium and plasma osmolality, as well as hepatic transaminitis. She underwent a computed tomography scan, which detected high liver density. Amiodarone-induced syndrome of inappropriate antidiuresis with hepatic transaminitis was diagnosed, and amiodarone was discontinued. After discharge, her hepatic transaminitis improved, and there was no recurrence of hyponatremia with a sign of somnolence. Amiodarone is an important drug used to treat ventricular arrhythmias. However, it has a variety of adverse effects. Syndrome of inappropriate antidiuresis is a rare complication of amiodarone. If hyponatremia occurs after starting amiodarone, this complication should be considered. Learning objective: Amiodarone is an important drug used to treat ventricular arrhythmias, such as ventricular tachycardia and ventricular fibrillation. However, amiodarone has a variety of adverse effects. Syndrome of inappropriate antidiuresis is a rare complication of amiodarone. If hyponatremia occurs after starting amiodarone, this complication should be considered.

Growth Differentiation Factor-15 and Clinical Outcomes in Japanese Patients With Ischemic Heart Disease.

Background: Despite a reduction in the rate of thrombotic events, ischemic heart disease (IHD) remains a key medical problem associated with high major bleeding and mortality in Asian patients with IHD. Growth differentiation factor (GDF)-15, a stress-response cytokine belonging to the transforming growth factor beta superfamily, is reportedly associated with poor clinical outcomes in Western patients with IHD. However, the clinical significance of GDF-15 in Asian patients with IHD has not yet been fully elucidated. Objectives: The aim of the present study was to examine the impact of serum GDF-15 on clinical outcomes in Japanese patients with IHD. Methods: Serum GDF-15 levels were evaluated in 632 consecutive patients with IHD. All patients were followed up for a median period of 2.8 years. The primary endpoint was the all-cause mortality rate. Secondary endpoints were major adverse cardiovascular events (MACE), heart failure (HF)-related rehospitalization, bleeding, and thrombotic events. Results: Serum GDF-15 levels were elevated in acute coronary syndrome, severe coronary artery disease, and the major Japanese version of the high bleeding risk criteria. Multivariate Cox proportional hazards regression analysis demonstrated that GDF-15 was an independent predictor of all-cause mortality, MACE, HF-related rehospitalizations, and bleeding events after adjusting for confounding risk factors but not for thrombotic events. Adding GDF-15 to risk factors significantly improved the net reclassification index and integrated discrimination improvement for all-cause deaths, MACE, HF-related rehospitalization, and bleeding events. Conclusions: Serum GDF-15 could be a feasible marker for major bleeding and adverse clinical outcomes in Japanese patients with IHD.

Impact of estimated plasma volume status on clinical outcomes in patients with lower extremity artery disease who underwent endovascular therapy.

Lower extremity artery disease (LEAD) is an arterial occlusive disease associated with high morbidity and mortality. Estimated plasma volume status (ePVS), a marker of plasma volume expansion and contraction, is gaining attention in the field of cardiovascular diseases. However, the impact of ePVS on the clinical outcomes of patients with LEAD remains unclear. We calculated ePVS using two different formulas, Kaplan-Hakim (KH-ePVS) and Duarte (D-ePVS), in 288 patients (mean age, 73 years; 77% male) with LEAD who underwent the first endovascular therapy (EVT), and prospectively followed them up between 2014 and 2019. All patients were divided into two groups based on the median ePVS values. The primary endpoints were composite events, including all-cause death and major adverse limb events (death/MALE). The median follow-up duration was 672 days. There were 183, 40 and 65 patients in Fontaine classes II, III, and IV, respectively. The median KH-ePVS and D-ePVS was 5.96 and 5.09, respectively. The ePVS significantly increased with advancing Fontaine classes. Kaplan-Meier analysis demonstrated that the high ePVS group had higher rates of death/MALE than the low ePVS group. Multivariate Cox proportional hazard analysis revealed that each ePVS was an independent predictor for death/MALE after adjusting for confounding risk factors. The prognostic ability for death/MALE was significantly improved by adding ePVS to the basic predictors. ePVS was associated with LEAD severity and clinical outcomes, suggesting that ePVS could be an additional risk factor for death/MALE in patients with LEAD who underwent EVT. We demonstrated that the association between ePVS and the clinical outcomes of patients with LEAD. The prognostic ability for death/MALE was significantly improved by adding ePVS to the basic predictors. LEAD lower extremity artery disease, MALE major adverse limb events, PVS plasma volume status.

Renal tubular damage and clinical outcome in heart failure with preserved ejection fraction and chronic kidney disease.

AIMS: Despite advances in heart failure (HF) treatment, HF with preserved ejection fraction (HFpEF) remains a health problem with a high mortality rate. HFpEF is composed of diverse phenogroups, of which patients with concomitant renal impairment have worse outcomes. Renal tubular damage (RTD) is associated with the development of HF and chronic kidney disease (CKD). However, the impact of RTD on HF progression in patients with HFpEF and CKD remains unclear. The aim of the present study was to examine whether RTD could predict HF-related events in patients with HFpEF and CKD. METHODS AND RESULTS: We measured RTD markers, such as urinary ß2 -microglobulin to creatinine ratio (UBCR) and N-acetyl-ß-d-glucosamidase (NAG) level, in 319 consecutive patients with HFpEF and CKD who were hospitalized for acute HF (49% females, mean age 76 ± 12). Based on previous reports, high UBCR and high NAG levels were defined as UBCR ≥300 µg/gCr and NAG >14.2 U/gCr, respectively. There were 91 HF-related events, defined as HF hospitalizations or HF deaths, during the median follow-up period of 5.2 years. The prevalence of high UBCR increased with advancing New York Heart Association functional class and albuminuria. Kaplan-Meier analysis demonstrated that patients with high UBCR had more HF-related events than those with normal or low UBCR. Multivariate Cox proportional hazards regression analyses demonstrated that high UBCR, but not high NAG level, was an independent predictor of HF-related events after adjusting for confounding risk factors in patients with HFpEF and CKD (hazard ratio, 2.60; 95% confidence interval, 1.52-4.72; P = 0.0009). UBCR significantly improved the C-statistic, with a significant net reclassification index and integrated discrimination improvement (0.738 vs. 0.684; P = 0.0244). CONCLUSION: RTD, as assessed by a high UBCR, was associated with the severity and clinical outcomes of HFpEF and CKD, indicating that it could be a feasible marker for HF progression.

Growth Differentiation Factor 15 and Clinical Outcomes in Japanese Patients With Heart Failure.

BACKGROUND: Heart failure (HF) is an increasing health problem associated with a high mortality rate. Growth differentiation factor (GDF) 15, a stress response cytokine belonging to the transforming growth factor-ß superfamily, is associated with poor clinical outcomes in a broad spectrum of cardiovascular diseases. However, the prognostic usefulness of GDF15 in Japanese patients with HF remains unclear.Methods and Results: We measured serum concentrations of GDF15 and B-type natriuretic peptide (BNP) in 1,201 patients with HF. All patients were prospectively followed for a median period of 1,309 days. In all, 319 HF-related events and 187 all-cause deaths occurred during the follow-up period. Kaplan-Meier analysis demonstrated that, among GDF15 tertiles, the highest tertile group had the greatest risk of HF-related events and all-cause mortality. Multivariate Cox proportional hazard regression analysis demonstrated that the serum GDF15 concentration was an independent predictor of HF-related events and all-cause deaths after adjusting for confounding risk factors. Serum GDF15 improved the prediction capacity for all-cause deaths and HF-related events with a significant net reclassification index and integrated discrimination improvement. Subgroup analysis in patients with HF with preserved ejection fraction also showed the prognostic usefulness of GDF15. CONCLUSIONS: Serum GDF15 concentrations were associated with HF severity and clinical outcomes, indicating that GDF15 could provide additional clinical information to track the health status of patients with HF.

Recurrent Takotsubo Syndrome Presenting with Different Ballooning Patterns and Electrocardiographic Abnormalities.

A 73-year-old woman presented with takotsubo syndrome with apical ballooning patterns after quarreling with her husband. Two years later, she was admitted to the hospital with chest pain after experiencing the same emotional stress. Her electrocardiogram showed different abnormalities compared to the previous event, and her left ventriculogram demonstrated takotsubo syndrome with mid-ventricular ballooning patterns. Recurrence of takotsubo syndrome with different ballooning patterns is rare. We herein report our experience with a patient who developed recurrent takotsubo syndrome with various ballooning patterns and different electrocardiographic abnormalities along with a literature review.

Prognostic impact of plasma xanthine oxidoreductase activity in patients with heart failure with atrial fibrillation.

BACKGROUND: Xanthine oxidoreductase (XOR) is a rate-limiting enzyme for uric acid (UA) production and plays an important role in generating reactive oxygen species (ROS). Overproduction of ROS is reported to contribute to the pathophysiology of atrial fibrillation (AF), however, the prognostic impact of plasma XOR activity in patients with heart failure (HF) with AF is undetermined. METHODS: We measured plasma XOR activity in 475 HF patients, including those with sinus rhythm (HF-SR, n = 211), and those with AF (HF-AF, n = 264). The type of AF included paroxysmal (n = 128) and persistent (n = 136) AF. All patients were prospectively followed up for a median period of 804 days. RESULTS: HF-AF patients had significantly higher plasma XOR activity and serum UA levels compared with HF-SR patients. Both plasma XOR activity and serum UA levels were higher in patients with persistent AF than in those with SR and with paroxysmal AF. Multivariate linear regression analysis showed that persistent AF was independently associated with increased XOR activity. During the follow-up period, there were 79 major adverse cardiovascular events (MACEs). HF-AF patients with MACEs had higher plasma XOR activity compared with those without MACEs, while there were no significant differences in serum UA levels. Multivariate Cox proportional analysis showed that high XOR activity was an independent risk factor for MACEs after adjustment for confounding factors. Kaplan-Meier analysis revealed that the high XOR activity group had a higher risk of MACEs than the low XOR activity group. The prediction model was significantly improved by the addition of XOR activity to the basic predictors. CONCLUSIONS: HF-AF patients had significantly higher plasma XOR activity compared with HF-SR patients. Plasma XOR activity proved to be a reliable indicator for MACEs in HF-AF patients.

A Case of Recurrent Infective Endocarditis Caused by Streptococcus Agalactiae.

A 53-year-old man was admitted to hospital with a high fever and shivering. He had undergone aortic valve replacement 4 years previously due to infective endocarditis caused by Streptococcus agalactiae. 18F-fluorodeoxyglucose positron emission tomography/CT (18F-FDG PET/CT) showed increased uptake in the tissue surrounding the prosthetic valve. S. agalactiae was detected in blood cultures after admission. We made a diagnosis of prosthetic valve endocarditis due to an S. agalactiae infection relapse. After 6 weeks of antibacterial treatment, the inflammatory findings successfully improved. However, reexamination with 18F-FDG PET/CT suggested the possibility of persistent prosthetic valve infection. Therefore, we decided to continue the oral antibiotic treatment after discharge.

A Body Shape Index and Aortic Disease-Related Mortality in Japanese General Population.

AIMS: Aortic diseases (ADs), including aortic dissection, aortic aneurysm, and aortic rupture, are fatal, with extremely high mortality rates. A body shape index (ABSI), an anthropometric measure calculated as waist circumference adjusted by height and weight, improves the predictive capacity for mortality. However, whether ABSI is a risk factor for AD-related mortality in the general population remains unclear. METHODS: We used a nationwide database of 630,842 individuals (aged 40-75 years) who participated in the annual "Specific Health Check and Guidance in Japan" between 2008 and 2010. RESULTS: During the follow-up period of 3.8 years, 159 AD-related deaths occurred, including 105 aortic dissections and 54 aortic aneurysm ruptures. The subjects were divided into three groups based on ABSI tertiles. Kaplan-Meier analysis demonstrated that the 3rd tertile (with the highest ABSI) had the greatest risk among the three groups. Multivariate Cox proportional hazard regression analysis demonstrated that ABSI was significantly associated with AD-related death after adjusting for confounding risk factors. Neither waist circumference nor body mass index consistently predicted AD-related death in the multivariate model. The prediction capacity was significantly improved by the addition of ABSI to the confounding risk factors. CONCLUSIONS: We demonstrated for the first time that ABSI, a surrogate marker for abdominal visceral fat tissue, was associated with AD-related deaths in the general population, suggesting the importance of central adiposity in the development of AD.

Disparity of Performance Measure by Door-to-Balloon Time Between a Rural and Urban Area for Management of Patients With ST-Segment Elevation Myocardial Infarction　- Insights From the Nationwide Japan Acute Myocardial Infarction Registry.

BACKGROUND: Although a door-to-balloon (D2B) time ≤90 min is recognized as a key indicator of timely reperfusion for patients with ST-segment elevation myocardial infarction (STEMI), it is unclear whether regional disparities in the prognostic value of D2B remain in contemporary Japan.Methods and Results: We retrospectively analyzed 17,167 STEMI patients (mean [±SD] age 68±13 years, 77.6% male) undergoing primary percutaneous coronary intervention. With reference to the Japanese median population density of 1,147 people/km2, patients were divided into 2 groups: rural (n=6,908) and urban (n=10,259). Compared with the urban group, median D2B time was longer (70 vs. 62 min; P<0.001) and the rate of achieving a D2B time ≤90 min was lower (70.7% vs. 75.4%; P<0.001) in the rural group. In-hospital mortality was lower for patients with a D2B time ≤90 min than >90 min, regardless of residential area, whereas multivariable analysis identified prolonged D2B time as a predictor of in-hospital death only in the rural group (adjusted odds ratio 1.57; 95% confidence interval 1.18-2.09; P=0.002). Importantly, the rural-urban disparity in in-hospital mortality emerged most distinctively among patients with Killip Class IV and a D2B time >90 min. CONCLUSIONS: These data suggest that there is a substantial rural-urban gap in the prognostic significance of D2B time among STEMI patients, especially those with cardiogenic shock and a prolonged D2B time.

Prognostic Impact of Renal Dysfunction at 1-Year Follow-Up on Clinical Outcomes After Percutaneous Coronary Intervention.

AIMS: Renal dysfunction is an independent predictor of adverse outcomes in patients with coronary artery disease (CAD). However, the prognostic impact of mid-term changes in renal dysfunction status remains unclear. This study aimed to investigate the impact of mid-term changes in renal dysfunction status on long-term clinical outcomes in CAD patients who underwent percutaneous coronary intervention (PCI). METHODS: We enrolled 382 consecutive patients with CAD who underwent PCI. Renal dysfunction was defined as a reduced estimated glomerular filtration rate (eGFR) of ＜60 mL/min/1.73m2. Renal dysfunction status was evaluated at baseline and 1-year follow-up after PCI. We divided the study population into three groups: persistent renal dysfunction, new-onset renal dysfunction, and no or improved renal dysfunction at 1-year follow-up as compared with on baseline. The endpoints of this study were composite events, including all-cause death, acute coronary syndrome, target vessel revascularization, and stroke. RESULTS: At baseline, renal dysfunction was observed in 77 patients (20%). At the 1-year follow-up, new-onset renal dysfunction was observed in 46 patients (12%), and 59 patients (15%) had persistent renal dysfunction. Kaplan-Meier analysis revealed a significantly higher event rate in patients with persistent renal dysfunction and new-onset renal dysfunction (log-rank test, P=0.0003). In the multivariate Cox proportional hazards analysis, persistent renal dysfunction and new-onset renal dysfunction were independently associated with composite events after adjusting for confounding factors (adjusted hazard ratios 4.08 and 2.64, 95% confidence intervals 1.72-9.57 and 1.03-6.31, P=0.0016, P=0.0045, respectively). CONCLUSION: Persistent and new-onset renal dysfunction at 1-year follow-up were associated with unfavorable outcomes in patients with CAD who underwent PCI.