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.

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.

Usefulness of Inter-Hospital Heart Team Conference Based Collaborative Outpatient Cardiac Rehabilitation in Patients with Cardiovascular Disease.

An inter-hospital heart team conference based collaborative follow-up (FU) may facilitate outpatient cardiac rehabilitation (CR) programs, especially in hospitals without an outpatient CR center. Consecutive 145 patients with cardiovascular disease who received inpatient treatment at Yamagata University Hospital were divided into collaborative (n = 76) and same-hospital (n = 69) FU groups. In the collaborative FU group, patients received outpatient care at a university hospital and outpatient CR at different hospitals. In the same-hospital FU group, patients received outpatient care and outpatient CR at the same hospital other than the university hospital. The collaborative FU group held monthly 60-minute inter-hospital heart team conferences with CR specialists. No cardiovascular accidents occurred during the outpatient CR program in either group. Peak oxygen uptake VO2, anaerobic threshold, brain natriuretic peptide level, and left ventricular ejection fraction significantly improved in both groups. Kaplan-Meier analysis revealed no significant difference in prognosis between the collaborative and same-hospital FU groups (P = 0.246). Of the patients who had collaborative CR programs, 29 (38.2%) patients (37 consultations) were discussed at an inter-hospital heart team conference. Eighteen (48.6%) consultations were for issues related to continuing outpatient CR programs. Collaborative FU was as useful as same-hospital FU in terms of safety, efficacy, and prognosis in patients with cardiovascular disease. We conclude that regular inter-hospital heart team conferences are useful for facilitating collaboration among outpatient CR programs.

Blood Pressure, Hypertension, and the Risk of Aortic Dissection Incidence and Mortality: Results From the J-SCH Study, the UK Biobank Study, and a Meta-Analysis of Cohort Studies.

BACKGROUND: Hypertension or elevated blood pressure (BP) is an important risk factor for aortic dissection (AD); however, few prospective studies on this topic have been published. We investigated the association between hypertension/elevated BP and AD in 2 cohorts and conducted a meta-analysis of published prospective studies, including these 2 studies. METHODS: We analyzed data from the J-SHC study (Japan-Specific Health Checkups) and UK Biobank, which prospectively followed up 534 378 and 502 424 participants, respectively. Multivariable Cox regression was used to estimate hazard ratios and 95% CIs for the association of hypertension/elevated BP with AD incidence in the UK Biobank and AD mortality in the J-SHC Study. In the meta-analysis, summary relative risks were calculated with random-effects models. A potential nonlinear dose-response relationship between BP and AD was tested with fractional polynomial models, and the best-fitting second-order fractional polynomial regression model was determined. RESULTS: In the J-SHC study and UK Biobank, there were 84 and 182 ADs during the 4- and 9-year follow-up, and the adjusted hazard ratios of AD were 3.57 (95% CI, 2.17-6.11) and 2.68 (95% CI, 1.78-4.04) in hypertensive individuals, 1.33 (95% CI, 1.05-1.68) and 1.27 (95% CI, 1.11-1.48) per 20-mm Hg increase in systolic BP (SBP), and 1.67 (95% CI, 1.40-2.00) and 1.66 (95% CI, 1.46-1.89) per 10-mm Hg increase in diastolic BP (DBP), respectively. In the meta-analysis, the summary relative risks were 3.07 (95% CI, 2.15-4.38, I2=76.7%, n=7 studies, 2818 ADs, 4 563 501 participants) for hypertension and 1.39 (95% CI, 1.16-1.66, I2=47.7%, n=3) and 1.79 (95% CI: 1.51-2.12, I2 = 57.0%, n=3) per 20-mm Hg increase in SBP and per 10-mm Hg increase in DBP, respectively. The AD risk showed a strong, positive dose-response relationship with SBP and even more so with DBP. The risk of AD in the nonlinear dose-response analysis was significant at SBP >132 mm Hg and DBP >75 mm Hg. CONCLUSIONS: Hypertension and elevated SBP and DBP are associated with a high risk of AD. The risk of AD was positively dose dependent, even within the normal BP range. These findings provide further evidence for the optimization of BP to prevent AD.

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.

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.

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.

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.

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.

One-year outcome after percutaneous coronary intervention in nonagenarians: Insights from the J-PCI OUTCOME registry.

BACKGROUND: Nonagenarian patients who undergo percutaneous coronary intervention (PCI) are increasing, and a few previous studies have reported their long-term outcomes. However, differences in their long-term outcomes between generations remain unclear. This study aimed to investigate 1-year all-cause and cardiovascular (CV) mortality, and major adverse cardiovascular events (MACE; cardiovascular death, myocardial infarction, and stroke) of nonagenarian patients who underwent PCI compared with the other elder patients, using a nationwide registration system. METHODS: The patient-level data registered between January 2017 and December 2017 was extracted from the J-PCI OUTCOME Registry endorsed by the Japanese Association of Cardiovascular Intervention and Therapeutics (CVIT). The one-year all-cause and cardiovascular (CV) mortality, MACE, and major bleeding events were identified. RESULTS: Out of 40,722 patients over 60 years of age, 880 (2.1%) were nonagenarians. For nonagenarians, the 1-year mortality rate was substantial (13.5%). The MACE and CV death rates were also high (8.1%, and 6.8%, respectively) for nonagenarians, and these event rates were approximately 1.5 times higher in nonagenarians than octogenarians. Multivariate regression analysis showed that presentation with cardiogenic shock [hazard ratio (HR) 2.32; 95 confidence intervals (CI): 1.22-4.41], or cardiac arrest (HR 2.91; 90% CI: 1.28-6.62), and use of oral anticoagulants (HR 2.10; 90% CI: 1.07-4.12) were the predictors of 1-year MACE. CONCLUSIONS: Even in the contemporary era, nonagenarians who have undergone PCI still face a considerably increased risk for adverse cardiovascular events that reduces long-term survival. In addition to having poorer lesion characteristics, adverse events, including death, MACEs, and major bleeding, occurred 1.5 times more frequently in nonagenarians than in octogenarians.

Association between thrombolysis in myocardial infarction grade and clinical outcome after emergent percutaneous coronary intervention in patients with acute myocardial infarction who have suffered out-of-hospital cardiac arrest: the Yamagata AMI registry.

Despite improvements in the survival rate of acute myocardial infarction (AMI), out-of-hospital cardiac arrest (OHCA) due to AMI is still a devastating condition. Thrombolysis in myocardial infarction (TIMI) grade is used to classify coronary reperfusion after percutaneous coronary intervention (PCI), but it remains unclear whether TIMI grade after emergent PCI is associated with short-term mortality in patients with AMI who have suffered OHCA. We analyzed data collected from 2012 to 2017 and recorded in the Yamagata AMI registry, which is a multicenter surveillance conducted in all institutions in Yamagata prefecture. Among 3332 patients with AMI, 254 had suffered OHCA. There were 564 deaths during the 30 days after the onset of AMI. The survival rate was lower in patients who had suffered OHCA than in those who had not (40% vs. 87%; P < 0.0001). Patients with AMI who had suffered OHCA were divided into three groups based on TIMI grade (TIMI III group, n = 70; TIMI ≤ II group, n = 21; and no coronary angiography [non-CAG] group, n = 163). The survival rates in the TIMI III, TIMI ≤ II, and non-CAG groups were 87%, 38%, and 5%, respectively. Kaplan-Meier analysis demonstrated that the survival rate was highest in the TIMI III group. Multivariate Cox proportional hazard regression analysis demonstrated that TIMI III was closely associated with survival after adjustment for confounding factors. Achieving TIMI grade III during emergent PCI is crucial to improve survival in patients with AMI who have suffered OHCA.

Albumin-to-globulin ratio predicts clinical outcomes of heart failure with preserved ejection fraction in women.

Despite advances in medicine, heart failure with preserved ejection fraction (HFpEF) remains an increasing health concern associated with a high mortality rate. Research has shown sex-based differences in the clinical characteristics of patients with HF; however, definitive biomarkers for poor clinical outcomes of HFpEF in women are unavailable. We focused on the albumin-to-globulin ratio (AGR), a biomarker for malnutrition and inflammation and investigated its usefulness as a predictor of clinical outcomes of HFpEF in women. We measured the AGR in consecutive 224 women with HFpEF and 249 men with HFpEF. There were 69 cardiac events in women with HFpEF and 69 cardiac events in men with HFpEF during the follow-up period. The AGR decreased with advancing New York Heart Association functional class in women with HFpEF. Patients were categorized into three groups based on AGR tertiles. Kaplan-Meier analysis showed that among the three groups, the risk for cardiac events and HF-associated rehospitalizations was the highest in the lowest tertile in women with HFpEF. Univariate and multivariate Cox proportional hazard regression analyses showed that after adjustment for confounding risk factors, the AGR was an independent predictor of cardiac events and HF-associated rehospitalizations in women with HFpEF, but not in men with HFpEF. The addition of AGR to the risk factors significantly improved the net reclassification and integrated discrimination indices in women with HFpEF. This is the first study that highlights the significant association between the AGR and the severity and clinical outcomes of HFpEF in women. Addition of AGR to the risk factors improved its prognostic value for clinical outcomes, which indicates that this variable may serve as a useful clinical biomarker for HFpEF in women.

Association of Nephronophthisis 4 genetic variation with cardiorenal syndrome and cardiovascular events in Japanese general population: the Yamagata (Takahata) study.

BACKGROUND: Nephronophthisis (NPHP) 4 gene encoding nephrocystin-4, which contributes to end-stage renal disease in children and young adults, is involved in the development of the heart and kidneys. Cardiorenal syndrome (CRS), which consists of bidirectional dysfunction of the heart and kidneys, is a risk factor for cardiovascular events. Single-nucleotide polymorphisms (SNPs) within the NPHP4 gene are reportedly associated with kidney function, even in adults. However, the association of NPHP4 gene variability with CRS and cardiovascular events remains unknown. METHODS AND RESULTS: This prospective cohort study included 2946 subjects who participated in a community-based health study with a 16-year follow-up period. We genotyped 11 SNPs within the NPHP4 gene whose minor allele frequency was greater than 0.1 in the Japanese population. The SNP rs12058375 was significantly associated with CRS and cardiovascular events. Multivariate logistic analysis demonstrated a significant association between the homozygous A-allele of rs12058375 with the presence of CRS. Haplotype analysis identified the haplotype with the A-allele of rs12058375 as an increased susceptibility factor for CRS. Kaplan-Meier analysis demonstrated that homozygous A-allele carriers of rs12058375 had the greatest risk of developing cardiovascular events among the NPHP4 variants. Multivariate Cox proportional hazard regression analysis revealed that the homozygous A-allele and heterozygous carriers of rs12058375 were associated with cardiovascular events after adjusting for confounding factors. The net reclassification index and integrated discrimination index were significantly improved by the addition of rs12058375 as a cardiovascular risk factor. CONCLUSION: Genetic variations in the NPHP4 gene were associated with CRS and cardiovascular events in the general population, suggesting that it may facilitate the early identification of high-risk subjects with CRS and cardiovascular events.

Ambulatory electrocardiographic markers predict serious cardiac events in patients with chronic kidney disease: The Japanese Noninvasive Electrocardiographic Risk Stratification of Sudden Cardiac Death in Chronic Kidney Disease (JANIES-CKD) study.

BACKGROUND: Noninvasive electrocardiographic markers (NIEMs) are promising arrhythmic risk stratification tools for assessing the risk of sudden cardiac death. However, little is known about their utility in patients with chronic kidney disease (CKD) and organic heart disease. This study aimed to determine whether NIEMs can predict cardiac events in patients with CKD and structural heart disease (CKD-SHD). METHODS: We prospectively analyzed 183 CKD-SHD patients (median age, 69 years [interquartile range, 61-77 years]) who underwent 24-h ambulatory electrocardiographic monitoring and assessed the worst values for ambulatory-based late potentials (w-LPs), heart rate turbulence, and nonsustained ventricular tachycardia (NSVT). The primary endpoint was the occurrence of documented lethal ventricular tachyarrhythmias (ventricular fibrillation or sustained ventricular tachycardia) or cardiac death. The secondary endpoint was admission for cardiovascular causes. RESULTS: Thirteen patients reached the primary endpoint during a follow-up period of 24 ± 11 months. Cox univariate regression analysis showed that existence of w-LPs (hazard ratio [HR] = 6.04, 95% confidence interval [CI]: 1.4-22.3, p = .007) and NSVT [HR = 8.72, 95% CI: 2.8-26.5: p < .001] was significantly associated with the primary endpoint. Kaplan-Meier analysis demonstrated that the combination of w-LPs and NSVT resulted in a lower event-free survival rate than did other NIEMs (p < .0001). No NIEM was useful in predicting the secondary endpoint, although the left ventricular mass index was correlated with the secondary endpoint. CONCLUSION: The combination of w-LPs and NSVT was a significant risk factor for lethal ventricular tachyarrhythmias and cardiac death in CKD-SHD patients.

Left Atrial Filling Time Index (LAFTI) Evaluated by 2D Speckle Tracking Echocardiography Predicts Poor Cardiac Prognosis in Patients with Heart Failure.

Left atrial (LA) dysfunction is known to be a more sensitive prognostic marker than left ventricular (LV) dysfunction in patients with heart failure (HF). Persistent LA overload increases LA stiffness which impairs LA relaxation. The aim of this study was to investigate whether LA filling time is associated with clinical outcomes in patients with HF. Two-dimensional speckle tracking echocardiography (2DSTE) was performed at discharge, to measure LA and LV strain in 179 HF patients admitted to our hospital. The LA filling time index (LAFTI) was defined as the time from onset of the R wave to the peak LA systolic strain divided by the R-R interval. All patients were prospectively followed with cardiac events including cardiac death and rehospitalization for HF. There were 64 cardiac events during a median follow-up period of 451 days. There were no significant differences in heart rate, severity of HF at discharge, etiology of HF, severity of mitral regurgitation, or LV global longitudinal strain between the cardiac event group and no cardiac event group. Patients with cardiac events had significantly higher levels of brain natriuretic peptide (BNP), ratio of the E wave to e' (E/e'), left atrial volume index (LAVI), and lower LAFTI than those without. Kaplan-Meier analysis showed that patients with lower LAFTI were associated with higher cardiac event rates. Multivariate Cox hazard analysis showed that LAFTI was independently associated with the cardiac events after adjustment for confounding factors. In conclusion, LAFTI is a feasible predictor for cardiac events in patients with HF.

Perfusion Balloon Is Useful for Preventing Obstruction of Left Main Coronary Artery During Transcatheter Aortic Valve Implantation.

The incidence of acute coronary obstruction during transcatheter aortic valve implantation (TAVI) is low (< 1.0%); however, it is associated with high mortality. An 83-year-old female with a history of chest pain and syncope was diagnosed with severe aortic stenosis. Computed tomography showed severely calcified aortic leaflets with a low left coronary ostial height of 7.8 mm, which indicates a high risk of coronary obstruction. TAVI was performed using the right femoral artery approach under general anesthesia. To prevent coronary obstruction and minimize coronary flow obstruction, coronary protection of the left main tract (LMT) via the left radial artery was established with a perfusion balloon. We crossed a 23 mm Sapien 3 transcatheter heart valve and settled it at an appropriate position on the aortic valve. After inflation of the perfusion balloon at the LMT, we started rapid ventricular pacing, and deployed the Sapien 3 using the KBI technique. Hemodynamics were stable and aortography showed excellent coronary flow with no stenosis of the LMT ostium. This strategy may serve as a useful method to prevent coronary obstruction and minimize coronary ischemia.

One-Year Change in Diastolic Blood Pressure and Aortic Disease-Related Mortality in a Japanese General Population Aged 50-75 Years.

BACKGROUND: Aortic diseases (ADs), including aortic dissection, aortic aneurysm, and aortic rupture, are fatal diseases with extremely high mortality rates. Hypertension has been reported to be associated with AD development; however, it remains unclear whether a 1-year change in diastolic blood pressure (DBP) is a risk factor for AD-related mortality in the general population.Methods and Results:This study used a nationwide database of 235,076 individuals (aged 50-75 years) who participated in the annual "Specific Health Check and Guidance in Japan" for 2 consecutive years between 2008 and 2010. There were 55 AD-related deaths during the follow-up period of 1,770 days. All subjects were divided into 4 groups based on the baseline DBP and change in DBP at 1 year: persistent high DBP, increasing DBP, decreasing DBP, and normal DBP. Kaplan-Meier analysis demonstrated that the persistent high DBP group had the greatest risk among the 4 groups. Multivariate Cox proportional hazard regression analysis demonstrated that both DBP and 1-year change in DBP were significantly associated with AD-related deaths. The prediction capacity was significantly improved by the addition of 1-year change in DBP to confounding risk factors. CONCLUSIONS: This study demonstrated for the first time that a 1-year change in DBP was associated with AD-related deaths in the general population. Monitoring changes in DBP are of critical importance in the primary prevention of AD-related deaths in apparently healthy subjects aged 50-75 years.

Prognostic significance of the controlling nutritional (CONUT) score in patients with acute coronary syndrome.

BACKGROUND: Malnutrition is an independent predictor of adverse outcomes in patients with acute coronary syndrome. The controlling nutritional (CONUT) score has been applied to assess nutritional status, and has been reported to be associated with poor prognosis in patients with heart failure. However, the prognostic impact of the CONUT score in patients with acute coronary syndrome (ACS) remains to be elucidated. METHODS: We evaluated the CONUT score in 196 patients with ACS who underwent percutaneous coronary intervention. We divided the patients into four groups according to CONUT score (undernutrition degree: normal, CONUT 0-1 (reference); mild, CONUT 2-4; moderate, CONUT 5-8; severe, CONUT 9-12). The endpoint of the present study was composite events including all-cause death, acute coronary syndrome, target vessel revascularization, and stroke. RESULTS: The median CONUT score was significantly higher in patients with composite events than in those without events (P = 0.0058). Kaplan-Meier analysis revealed that a significantly higher event rate in patients with severe malnutrition (log-rank test, P = 0.0222). In the multivariate Cox proportional hazards analysis, CONUT score was independently associated with composite events after adjustment for confounding factors (adjusted hazard ratio 1.284, 95% confidence interval 1.126-1.457, P = 0.0003). CONCLUSION: Higher CONUT scores were associated with unfavorable outcomes in patients with ACS. Malnutrition assessed by the CONUT score may provide valuable prognostic information in patients with ACS.

Impact of pre-operative coronary artery disease on the clinical outcomes of patients with aortic aneurysms.

Aortic aneurysm is an increasingly important public health problem with high morbidity and mortality. It is associated with coronary artery disease (CAD), which is a comorbidity of high incidence that is reported to worsen perioperative complications and long-term clinical outcomes in patients with an aortic aneurysm. Patients with significant coronary artery stenosis may require coronary revascularization and/or optimal medical therapy in the perioperative period of aneurysm surgery. However, the prognostic impact of non-significant coronary artery stenosis not indicated for coronary revascularization on clinical outcomes of patients with aortic aneurysms remains unclear. We performed coronary angiography on 239 consecutive patients with thoracic and abdominal aortic aneurysms before endovascular aortic repair or surgical repair. The patients were divided into the following 3 groups according to the severity of stenosis of major coronary arteries: non-CAD group (with < 25% stenosis), non-significant CAD group (with ≥ 25% but < 75% stenosis), and significant CAD group (with ≥ 75% stenosis). CAD was diagnosed in 133 (56%) patients consisting of 48 (20%) patients with non-significant CAD and 85 (36%) patients with significant CAD. Thirty-nine major adverse cardiovascular and cerebrovascular events (MACCEs) occurred in a median follow-up period of 723 days. Kaplan-Meier analysis revealed that the risk of MACCEs was higher in the significant and non-significant CAD groups than in the non-CAD group. Multivariate Cox proportional hazard regression analysis showed that the risk of MACCEs was equally high in the non-significant CAD and significant CAD groups compared to that in the non-CAD group after adjustment for confounding factors. CAD is significantly associated with poor outcomes in patients with aortic aneurysms, irrespective of the significance of CAD.

The Role of HECT-Type E3 Ligase in the Development of Cardiac Disease.

Despite advances in medicine, cardiac disease remains an increasing health problem associated with a high mortality rate. Maladaptive cardiac remodeling, such as cardiac hypertrophy and fibrosis, is a risk factor for heart failure; therefore, it is critical to identify new therapeutic targets. Failing heart is reported to be associated with hyper-ubiquitylation and impairment of the ubiquitin-proteasome system, indicating an importance of ubiquitylation in the development of cardiac disease. Ubiquitylation is a post-translational modification that plays a pivotal role in protein function and degradation. In 1995, homologous to E6AP C-terminus (HECT) type E3 ligases were discovered. E3 ligases are key enzymes in ubiquitylation and are classified into three families: really interesting new genes (RING), HECT, and RING-between-RINGs (RBRs). Moreover, 28 HECT-type E3 ligases have been identified in human beings. It is well conserved in evolution and is characterized by the direct attachment of ubiquitin to substrates. HECT-type E3 ligase is reported to be involved in a wide range of human diseases and health. The role of HECT-type E3 ligases in the development of cardiac diseases has been uncovered in the last decade. There are only a few review articles summarizing recent advancements regarding HECT-type E3 ligase in the field of cardiac disease. This study focused on cardiac remodeling and described the role of HECT-type E3 ligases in the development of cardiac disease. Moreover, this study revealed that the current knowledge could be exploited for the development of new clinical therapies.