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.

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.

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.

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.

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 impact of kidney dysfunction categorized by urinary to serum creatinine ratio on clinical outcomes in patients with heart failure.

Kidney dysfunction (KD) is closely associated with poor clinical outcome in patients with heart failure (HF). KD is classified as intrinsic and pre-renal KD. However, the impact of each KD on the clinical outcome in patients with HF has not yet been fully elucidated. We measured the urinary to serum creatinine (UC/SC) ratio, a marker for intrinsic and pre-renal KD, in 1009 consecutive patients with HF at admission. There were 314 cardio-renal events including HF and advanced end-stage renal dysfunction during the median follow-up period of 1154 days. There were 63 (6%) patients with intrinsic KD (UC/SC ratio < 20), 118 (12%) patients with intermediate KD (UC/SC ratio 20-40), 607 (60%) patients with pre-renal KD (UC/SC ratio > 40), and 221 (22%) patients with no KD. Multivariate Cox's proportional hazard regression analysis demonstrated that intrinsic and intermediate KDs were significantly associated with poor clinical outcome. The prediction model for cardio-renal events was significantly improved by the addition of UC/SC ratio to the confounding risk factors. Subgroup analysis in patients with HF with severely reduced glomerular filtration rates showed that the prevalence rates of intrinsic, intermediate, and pre-renal KDs were 23%, 30%, and 47%, respectively. The cardio-renal event rate was the highest in the intrinsic KD group compared with that in the other groups. Intrinsic KD was closely associated with extremely poor clinical outcome in patients with HF. The UC/SC ratio could provide important clinical information for the treatment and management of KD in patients with HF.

Prolonged total atrial conduction time evaluated with tissue Doppler imaging predicts poor cardiac prognosis in patients with heart failure.

Prolonged total atrial conduction time is caused by atrial remodeling. Left atrial remodeling is associated with poor outcome in patients with heart failure (HF). This study aimed to investigate whether prolonged total atrial conduction time predicts poor prognosis in patients with HF. We performed transthoracic echocardiography in 100 patients (65 men; mean age 68 ± 13 years) who were hospitalized for HF. Total atrial conduction time was defined as the duration from P wave onset on electrocardiography to peak A' wave on tissue Doppler imaging (TDI) echocardiography (PA-TDI duration). There were 37 cardiac events (37%) during a median follow-up period of 414 days. The PATDI duration was significantly longer in patients with cardiac events than in those without (150 ± 18 ms vs 133 ± 19 ms; P < 0.05). There were no significant differences in left ventricular end-diastolic dimensions and ejection fractions between patients with and without cardiac events. Patients with HF were divided into 3 groups according to tertiles of the PA-TDI duration. Kaplan-Meier analysis showed that the highest tertile of PA-TDI duration was associated with the greatest risk among patients with HF. Multivariate Cox proportional hazard analysis showed that the PA-TDI duration was an independent predictor of cardiac events, leading to the conclusion that prolonged PA-TDI duration was a feasible predictor of cardiac prognosis in patients with HF.

Direct comparison of prognostic ability of cardiac biomarkers for cardiogenic stroke and clinical outcome in patients with stroke.

Despite many recent advances in medicine, cardiogenic stroke is still a health problem with a high mortality rate. Cardiac biomarkers have been reported to be useful indicators for cardiogenic stroke and subsequent cerebrovascular events. However, there are no data directly comparing the cardiac biomarkers in stroke patients. We measured atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), N-terminal pro-brain natriuretic peptide (NT-proBNP), and high-sensitivity troponin T (hsTnT) levels and performed transthoracic and transesophageal echocardiography in 282 stroke patients. There were 108 cases of cardiogenic stroke and 47 cases of major adverse cardiovascular and cerebrovascular events (MACCE) during the follow-up period. Association with left atrial function and left atrial appendage function appeared somewhat stronger for BNP and NT-proBNP than ANP and hsTnT. Multivariate logistic analysis demonstrated that cardiac biomarkers excluding ANP were significantly associated with cardiogenic stroke in stroke patients, multivariate Cox's proportional hazards regression analysis demonstrated that all biomarkers were significantly associated with MACCE after adjustment for confounding risk factors. Receiver operating characteristic curve analysis showed that the C indices of BNP and NT-proBNP for cardiogenic stroke and MACCE were almost equal, but significantly greater than those of ANP and hsTnT. Both BNP and NT-proBNP levels are useful predictors of cardiogenic stroke and subsequent MACCE superior to ANP and hsTnT in stroke patients.

Left atrial remodeling index is a feasible predictor of poor prognosis in patients with acute ischemic stroke.

Left atrial (LA) functional remodeling as well as LA structural remodeling are associated with incident LA appendage (LAA) thrombus formation. This study aimed to elucidate whether combined assessment of LA functional and structural remodeling can predict LAA dysfunction and recurrent cerebrovascular events in patients with acute ischemic stroke. We performed transthoracic and transesophageal echocardiography in 196 patients within 7 days after acute ischemic stroke. Peak systolic LA strain was evaluated using 2D speckle tracking imaging. We defined the ratio of LA peak systolic strain to LA volume index (LAVI) as the LA remodeling index (LARI). All patients were prospectively followed for recurrent cerebrovascular events. We divided patients into four groups according based on the LARI quartile. LAA dysfunction increased with decreasing LARI. In total, 52 recurrent cerebrovascular events were noted during the median follow-up period of 700 days. Patients with recurrent cerebrovascular events had lower LARI than those without recurrent events (0.50 ± 0.45 vs. 1.10 ± 0.95, P < 0.001). Kaplan-Meier analysis showed that patients with lower LARI were more susceptible to recurrent cerebrovascular events than those with higher LARI. Multivariate Cox proportional hazard regression analysis showed that LARI was an independent predictor of recurrent cerebrovascular events after adjustment for confounding factors. Net reclassification index improved with the addition of LARI to basic predictors. LARI is a novel feasible parameter for LAA dysfunction and can predict recurrent cerebrovascular events in patients with acute ischemic stroke.

Increased plasma xanthine oxidoreductase activity deteriorates coronary artery spasm.

Increased reactive oxygen species (ROS) contributes to the development of endothelial dysfunction, which is involved in coronary artery spasm (CAS). Xanthine oxidoreductase (XOR) plays a pivotal role in producing both uric acid and ROS. However, the association between plasma XOR activity and CAS has not been elucidated. The aim of this study was to investigate whether plasma XOR activity is associated with CAS. We measured XOR activity in 104 patients suspected for CAS, who presented without significant coronary artery stenosis and underwent intracoronary acetylcholine provocation tests. CAS was provoked in 44 patients and they had significantly higher XOR activity as compared with those without CAS. The patients were divided into three groups based on the XOR activity. The prevalence rate of CAS was increased with increasing XOR activity. A multivariate logistic regression analysis showed that the 3rd tertile group exhibited a higher incidence of CAS as compared with the 1st tertile group [odds ratio (OR) 6.9, P = 0.001) and the 2nd tertile group (OR 3.2, P = 0.033) after adjustment for conventional CAS risk factors, respectively. The C index was significantly improved by the addition of XOR activity to the baseline model based on CAS risk factors. Furthermore, the 3rd tertile group had the highest incidence of severe spasm defined as total obstruction, flow-limiting stenosis, diffuse spasm, multivessel spasm, and/or lethal arrhythmia. This is a first report to elucidate the association of plasma XOR activity with CAS. Increased plasma XOR activity is significantly associated with CAS.

Decreased Psoas Muscle Computed Tomography Value Predicts Poor Outcome in Peripheral Artery Disease.

BACKGROUND: The prognosis of peripheral artery disease (PAD) and comorbid sarcopenia is poor. Some reports indicate that the computed tomography (CT) value of skeletal muscle, which reflects intramuscular fat deposition as well as skeletal muscle mass, is considered a marker of sarcopenia. However, it remains unclear if skeletal muscle area and CT value are associated with poor outcomes in patients with PAD. Methods and Results: Psoas muscle area and CT value were measured by manual trace at the level of the third lumbar vertebral body in 327 consecutive patients with PAD undergoing endovascular therapy (EVT). The endpoint was major adverse cardiovascular and limb events (MACLE). There were 60 MACLE during the follow-up period. Patients with MACLE had lower mean psoas muscle CT value than those without. However, there was no significant difference in total psoas muscle area between patients with and without MACLE. Kaplan-Meier analysis demonstrated that the lowest tertile of psoas muscle CT value was associated with the highest risk of MACLE. Multivariate Cox hazard analysis revealed that psoas muscle CT value was associated with MACLE after adjustment for Fontaine class, previous ischemic heart disease, prevalence of diabetes mellitus, brain natriuretic peptide, and serum albumin. CONCLUSIONS: Psoas muscle CT value is a feasible predictor of MACLE in patients with PAD.

Circulating Surfactant Protein-D Is Associated With Clinical Outcomes in Peripheral Artery Disease Patients Following Endovascular Therapy.

BACKGROUND: Peripheral artery disease (PAD) is a risk factor for the development of cardiovascular disease and death. Surfactant protein-D (SP-D) is a 43-kDa protein secreted from type II pneumocytes in the lungs. Recent studies have demonstrated that circulating SP-D plays a key role in the development of atherosclerosis and is related to clinical outcomes in patients with ischemic heart disease. However, it remains unclear whether circulating SP-D is associated with clinical outcomes in patients with PAD.Methods and Results:We enrolled 364 patients with PAD who underwent endovascular therapy. We measured serum levels of SP-D and Krebs von den Lungen-6 (KL-6). During a median follow-up period of 974 days, there were 69 major adverse cardiovascular and leg events (MACLE), including 48 major adverse cardiovascular events (MACE). Kaplan-Meier analysis demonstrated that patients with high SP-D (≥110 ng/mL) had higher rates of MACE and MACLE than those with low SP-D. Multivariate Cox proportional hazard regression analysis demonstrated that SP-D, but not KL-6, was an independent predictor of MACE and MACLE. The addition of SP-D to known risk factors significantly improved the C index and net reclassification index. The circulating SP-D level was affected by sex, diabetes mellitus, and cilostazol prescription. CONCLUSIONS: Circulating SP-D was associated with clinical outcomes in patients with PAD, suggesting that it may be a new therapeutic target in these patients.

Impact of Objective Malnutrition Status on the Clinical Outcomes in Patients With Peripheral Artery Disease Following Endovascular Therapy.

BACKGROUND: Peripheral artery disease (PAD) is an athero-occlusive disease and a known risk factor for cardiovascular events. The controlling nutritional status (CONUT) score and geriatric nutritional risk index (GNRI) are objective tools for evaluating malnutrition and are reportedly associated with poor clinical outcomes in patients with fatal diseases. However, the effect of malnutrition on the clinical outcomes in patients with PAD remains unclear.Methods and Results:We enrolled 357 patients with PAD who underwent endovascular therapy. Malnutrition was diagnosed by CONUT score and GNRI as in previous reports. During a median follow-up period of 1,071 days, there were 67 major adverse cardiovascular and leg events (MACLEs). The CONUT score- and GNRI-based malnutrition statuses were identified in 56% and 46% of the patients, respectively. Proportion of malnutrition increased with advancing Fontaine class. The multivariate Cox proportional hazard regression analysis demonstrated that both the CONUT score- and GNRI-based malnutrition status was an independent predictor of MACLEs. The Kaplan-Meier analysis demonstrated that the MACLE ratio increased with deteriorating malnutrition. Finally, the addition of the CONUT score or GNRI to the known risk factors significantly improved the net reclassification index and integrated discrimination index. CONCLUSIONS: Malnutrition was common and closely associated with the clinical outcomes in patients with PAD, indicating that it is a novel therapeutic target in the management of these patients.

Biatrial volume, estimated using magnetic resonance imaging, predicts atrial fibrillation recurrence after ablation.

INTRODUCTION: The predictive value of left atrial volume (LAV) in atrial fibrillation (AF) is known, but the relationship of right atrial volume (RAV) and biatrial volume (BAV) with AF recurrence after pulmonary vein isolation (PVI) is not clear. Cardiac magnetic resonance (CMR) imaging allows us to more precisely quantify atrial volume. We investigated LAV, RAV, and BAV as predictors of AF recurrence following PVI in AF patients. METHODS AND RESULTS: We assessed 100 AF patients (age = 59.8 ± 9.5 years, 74 males, 26 females) who underwent nonenhanced CMR before their first PVI. LAV and RAV were measured using CMR. All patients were in sinus rhythm during CMR. BAV was calculated as the sum of LAV and RAV. During the 8-month follow-up, AF recurrence occurred in 23 patients. LAV, RAV, and BAV were significantly greater in patients with AF recurrence than in those without (LAV, 103.7 ± 25.8 vs 81.8 ± 24.2 mL, P < 0.001; RAV, 109.4 ± 27.0 vs 82.2 ± 19.6 mL, P < 0.001; BAV, 213.1 ± 46.7 vs 164.1 ± 38.7 mL, P < 0.001). Multivariate logistic regression analysis revealed that increased LAV, RAV, and BAV were significantly correlated with AF recurrence. The area under the receiver operation characteristic curve for BAV showed the largest value compared to that of LAV or RAV alone. CONCLUSIONS: LAV, RAV, and BAV were independent predictors of AF recurrence after PVI. Quantifying BAV may additionally improve prognostic stratification compared with LAV or RAV.

Impact of reduced forced expiratory volume on cardiac prognosis in patients with chronic heart failure.

In patients with chronic heart failure (CHF), comorbidity of airflow limitation is associated with poor outcomes. The forced expiratory volume in 1 s (FEV1) is used to evaluate the severity of airflow limitation. However, the impact of FEV1 severity on prognosis has only been partially elucidated in patients with CHF. In total, 248 consecutive patients with CHF who successfully fulfilled spirometric measurement criteria were enrolled and prospectively followed. Percent predicted FEV1 (FEV1%predicted) was associated with the New York Heart Association Functional Classification. FEV1%predicted was significantly associated with diastolic dysfunction, evaluated using echocardiography; elevated inflammation markers; and increased pulmonary arterial pressure. There were 60 cardiac events, including 9 cardiac-related deaths and 51 re-hospitalizations due to the exacerbation of CHF during a follow-up period. Kaplan-Meier analysis revealed that the lowest FEV1%predicted group had the highest event rate, irrespective of the presence of smoking history. Multivariate Cox proportional hazard analysis showed that FEV1%predicted was an independent predictor of cardiac events after adjusting for confounders. The net reclassification improvement and integrated discrimination improvement were improved by the addition of FEV1%predicted to other cardiac risk factors. Decreased FEV1%predicted was independently associated with the poor cardiac outcomes in patients with CHF.