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Background: Physical frailty and malnutrition coexist in older patients with heart failure (HF) and form a vicious cycle exacerbating each other and can cause poor clinical outcomes. We aimed to clarify the association of prevalence of physical frailty and malnutrition and clinical outcomes in hospitalized patients with HF. Methods: A total of 862 hospitalized patients aged ≥65 years with HF decompensation were included in this FRAGILE-HF post-hoc sub-analysis. Patients were categorized into Neither, Either, or Both groups based on the prevalence of physical frailty and malnutrition. The primary outcome was all-cause mortality within 1 year after discharge. Prognoses among the groups were compared in the entire cohort and in subgroups with preserved ejection fraction (pEF) and reduced/mildly reduced left ventricular ejection fractions (rEF/mrEF). Results: The Neither, Either, and Both groups comprised 32 %, 40 %, and 28 % respectively. During a 1-year follow-up period, 101 (12 %) patients died. Kaplan–Meier analysis showed significant differences in the primary outcomes among the groups (P

Abstract Aims MitraScore is a novel, simple, and manually calculatable risk score developed as a prognostic model for patients undergoing transcatheter edge‐to‐edge repair (TEER) for mitral regurgitation. As its components are considered prognostic in heart failure (HF), we aimed to investigate the usefulness of the MitraScore in HF patients. Methods and results We calculated MitraScore for 1100 elderly patients (>65 years old) hospitalized for HF in the prospective multicentre FRAGILE‐HF study and compared its prognostic ability with other simple risk scores. The primary endpoint was all‐cause deaths, and the secondary endpoints were the composite of all‐cause deaths and HF rehospitalization and cardiovascular deaths. Overall, the mean age of 1100 patients was 80 ± 8 years, and 58% were men. The mean MitraScore was 3.2 ± 1.4, with a median of 3 (interquartile range: 2–4). A total of 326 (29.6%), 571 (51.9%), and 203 (18.5%) patients were classified into low‐, moderate‐, and high‐risk groups based on the MitraScore, respectively. During a follow‐up of 2 years, 226 all‐cause deaths, 478 composite endpoints, and 183 cardiovascular deaths were observed. MitraScore successfully stratified patients for all endpoints in the Kaplan–Meier analysis (P

Abstract Aims Empagliflozin, a sodium‐glucose co‐transporter 2 inhibitor, was shown to be effective in patients with heart failure with preserved ejection fraction (HFpEF) in the EMPEROR‐Preserved trial. The present study aims to evaluate the cost‐effectiveness of empagliflozin among Japanese patients with HFpEF. Methods and results A Markov cohort model was developed to evaluate the cost‐effectiveness of empagliflozin added to standard of care (SoC) compared with SoC alone in patients with HFpEF from the perspective of the Japanese healthcare system and with a lifetime horizon. In addition to clinical events, the progression of disease severity was modelled based on the migration of Kansas City Cardiomyopathy Questionnaire‐Clinical Summary Scores (KCCQ‐CSS). Model inputs, including risk of clinical events, costs, and utilities/disutilities, were derived from EMPEROR‐Preserved trial data, a claims database and published literature. The generalizability of model results was investigated by applying various subgroups including age, body mass index (BMI), and region Asia, based on the subgroup analysis of EMPEROR‐Preserved data. In the base‐case analysis, empagliflozin yielded additional quality‐adjusted life years (QALYs; 0.11) with an incremental cost of $1408 per patient for Japanese patients with HFpEF. Incremental cost, mainly derived from drug acquisition cost ($1963 per patient), was largely offset by reduced cost in hospitalization for heart failure (HHF) and cardiovascular death (−$537 per patient and −$166 per patient, respectively). Treatment of empagliflozin provided incremental 0.11 QALYs and 0.08 life years compared with SoC alone. The incremental cost‐effectiveness ratio (ICER) was $12 772 (¥1 662 689)/QALY, which was below the Japanese willingness‐to‐pay (WTP) threshold of $38 408 (¥5 000 000)/QALY. The results were consistent across all the subgroups considered, and empagliflozin was dominant over SoC alone in the region Asia and BMI

Background Social factors encompass a broad spectrum of nonmedical factors, including objective (social isolation [SI]) and perceived (loneliness) conditions. Although social factors have attracted considerable research attention, information regarding their impact on patients with heart failure is scarce. We aimed to investigate the prognostic impact of objective SI and loneliness in older patients with heart failure. Methods and Results This study was conducted using the FRAGILE‐HF (Prevalence and Prognostic Value of Physical and Social Frailty in Geriatric Patients Hospitalized for Heart Failure; derivation cohort) and Kitasato cohorts (validation cohort), which included hospitalized patients with heart failure aged ≥65 years. Objective SI and loneliness were defined using the Japanese version of Lubben Social Network Scale‐6 and diagnosed when the total score for objective and perceived questions on the Lubben Social Network Scale‐6 was below the median in the FRAGILE‐HF. The primary outcome was 1‐year death. Overall, 1232 and 405 patients in the FRAGILE‐HF and Kitasato cohorts, respectively, were analyzed. Objective SI and loneliness were observed in 57.8% and 51.4% of patients in the FRAGILE‐HF and 55.4% and 46.2% of those in the Kitasato cohort, respectively. During the 1‐year follow‐up, 149 and 31 patients died in the FRAGILE‐HF and Kitasato cohorts, respectively. Cox proportional hazard analysis revealed that objective SI, but not loneliness, was significantly associated with 1‐year death after adjustment for conventional risk factors in the FRAGILE‐HF. These findings were consistent with the validation cohort. Conclusions Objective SI assessed using the Lubben Social Network Scale‐6 may be a prognostic indicator in older patients with heart failure. Given the lack of established SI assessment methods in this population, further research is required to refine such methods.

Abstract Background Cachexia substantially impacts the prognosis of patients with heart failure (HF); however, there is no standard method for cachexia diagnosis. This study aimed to investigate the association of Evans's criteria, consisting of multiple assessments, with the prognosis of HF in older adults. Methods This study is a secondary analysis of the data from the FRAGILE‐HF study, a prospective multicentre cohort study that enrolled consecutive hospitalized patients aged ≥65 years with HF. Patients were divided into two groups: the cachexia and non‐cachexia groups. Cachexia was defined according to Evans's criteria by assessing weight loss, muscle weakness, fatigue, anorexia, a decreased fat‐free mass index and an abnormal biochemical profile. The primary outcome was all‐cause mortality, as assessed in the survival analysis. Results Cachexia was present in 35.5% of the 1306 enrolled patients (median age [inter‐quartile range], 81 [74–86] years; 57.0% male); 59.6%, 73.2%, 15.6%, 71.0%, 44.9% and 64.6% had weight loss, decreased muscle strength, a low fat‐free mass index, abnormal biochemistry, anorexia and fatigue, respectively. All‐cause mortality occurred in 270 patients (21.0%) over 2 years. The cachexia group (hazard ratio [HR], 1.494; 95% confidence interval [CI], 1.173–1.903; P = 0.001) had a higher mortality risk than the non‐cachexia group after adjusting for the severity of HF. Cardiovascular and non‐cardiovascular deaths occurred in 148 (11.3%) and 122 patients (9.3%), respectively. The adjusted HRs for cachexia in cardiovascular mortality and non‐cardiovascular mortality were 1.456 (95% CI, 1.048–2.023; P = 0.025) and 1.561 (95% CI, 1.086–2.243; P = 0.017), respectively. Among the cachexia diagnostic criteria, decreased muscle strength (HR, 1.514; 95% CI, 1.095–2.093; P = 0.012) and low fat‐free mass index (HR, 1.424; 95% CI, 1.052–1.926; P = 0.022) were significantly associated with high all‐cause mortality, but there was no significant association between weight loss alone (HR, 1.147; 95% CI, 0.895–1.471; P = 0.277) and all‐cause mortality. Conclusions Cachexia evaluated by multi‐assessment was present in one third of older adults with HF and was associated with a worse prognosis. A multimodal assessment of cachexia may be helpful for risk stratification in older patients with HF.

Abstract Aims Frailty is highly prevalent and associated with poor prognoses in elderly patients with heart failure (HF). However, the potential effects of physical frailty on the benefits of HF medications in elderly patients with HF are unclear. We aimed to determine the influence of physical frailty on the prognosis of HF medications in elderly patients with HF with reduced and mildly reduced ejection fraction (HFr/mrEF). Methods and results From the combined HF database of the FRAGILE‐HF and Kitasato cohorts, hospitalized HF patients with a left ventricular ejection fraction

IntroductionHeart failure (HF) is an advanced stage of cardiac disease and is associated with a high rate of mortality. Previous studies have shown that sleep apnea (SA) is associated with a poor prognosis in HF patients. Beneficial effects of PAP therapy that is effective on reducing SA on cardiovascular events, were not yet established. However, a large-scale clinical trial reported that patients with central SA (CSA) which was not effectively suppressed by continuous positive airway pressure (CPAP) revealed poor prognosis. We hypothesize that unsuppressed SA by CPAP is associated with negative consequences in patients with HF and SA, including either obstructive SA (OSA) or CSA.MethodsThis was a retrospective observational study. Patients with stable HF, defined as left ventricular ejection fraction of ≤50%; New York Heart Association class ≥ II; and SA [apnea–hypopnea index (AHI) of ≥15/h on overnight polysomnography], treated with CPAP therapy for 1 month and performed sleep study with CPAP were enrolled. The patients were classified into two groups according to AHI on CPAP (suppressed group: residual AHI ≥ 15/h; and unsuppressed group: residual AHI

Abstract Background The purpose of this study was to clarify the prevalence, association with frailty and exercise capacity, and prognostic implication of sarcopenic obesity in patients with heart failure. Methods The present study included 779 older adults hospitalized with heart failure (median age: 81 years; 57.4% men). Sarcopenia was diagnosed based on the guidelines by the Asian Working Group for Sarcopenia. Obesity was defined as the percentage of body fat mass (FM) obtained by bioelectrical impedance analysis. The FM cut-off points for obesity were 38% for women and 27% for men. The primary endpoint was 1-year all-cause death. We assessed the associations of sarcopenic obesity occurrence with the short physical performance battery (SPPB) score and 6-minute walk distance (6MWD). Results The rates of sarcopenia and obesity were 19.3 and 26.2%, respectively. The patients were classified into the following groups: non-sarcopenia/non-obesity (58.5%), non-sarcopenia/obesity (22.2%), sarcopenia/non-obesity (15.3%), and sarcopenia/obesity (4.0%). The sarcopenia/obesity group had a lower SPPB score and shorter 6MWD, which was independent of age and sex (coefficient, − 0.120; t-value, − 3.74; P

Abstract Aims Although evidence suggests that cognitive decline and physical frailty in elderly patients with heart failure (HF) are associated with prognosis, the impact of concurrent physical frailty and cognitive impairment, that is, cognitive frailty, on prognosis has yet to be fully investigated. The current study sought to investigate the prevalence and prognostic impact of cognitive frailty in elderly patients with HF. Methods and results This study is a sub‐analysis of FRAGILE‐HF, a prospective multicentre observational study involving patients aged ≥65 years hospitalized for HF. The Fried criteria and Mini‐Cog were used to diagnose physical frailty and cognitive impairment, respectively. The association between cognitive frailty and the combined endpoint of mortality and HF rehospitalization within 1 year was then evaluated. Among the 1332 patients identified, 1215 who could be assessed using Mini‐Cog and the Fried criteria were included in this study. Among those included, 279 patients (23.0%) had cognitive frailty. During the follow‐up 1 year after discharge, 398 combined events were observed. Moreover, cognitive frailty was determined to be associated with a higher incidence of combined events (log‐rank: P = 0.0146). This association was retained even after adjusting for other prognostic factors (hazard ratio: 1.55, 95% confidence interval: 1.13–2.13). Furthermore, a sensitivity analysis using grip strength, short physical performance battery, and gait speed to determine physical frailty instead of the Fried criteria showed similar results. Conclusions This cohort study found that 23% of elderly patients with HF had cognitive frailty, which was associated with a 1.55‐fold greater risk for combined events within 1 year compared with patients without cognitive frailty.

Abstract Aims A patient's understanding of his or her own comorbidities is part of the recommended patient education for those with heart failure. The accuracy of patients' understanding of their comorbidities and its prognostic impact have not been reported. Methods and results Patients hospitalized for heart failure (n = 1234) aged ≥65 years (mean age: 80.1 ± 7.7 years; 531 females) completed a questionnaire regarding their diagnoses of diabetes, malignancy, stroke, hypertension, chronic obstructive pulmonary disease (COPD), and coronary artery disease (CAD). The patients were categorized into three groups based on the number of agreements between self‐reported comorbidities and provider‐reported comorbidities: low (1–2, n = 19); fair (3–4, n = 376); and high (5–6, n = 839) agreement groups. The primary outcome was a composite of all‐cause mortality or heart failure rehospitalization at 1 year. The low agreement group had more comorbidities and a higher prevalence of a history of heart failure. The agreement was good for diabetes (κ = 0.73), moderate for malignancy (κ = 0.56) and stroke (κ = 0.50), and poor‐to‐fair for hypertension (κ = 0.33), COPD (κ = 0.25), and CAD (κ = 0.30). The fair and low agreement groups had poorer outcomes than the good agreement group [fair agreement group: hazard ratio (HR): 1.25; 95% confidence interval (CI): 1.01–1.56; P = 0.041; low agreement group: HR: 2.74: 95% CI: 1.40–5.35; P = 0.003]. Conclusions The ability to recognize their own comorbidities among older patients with heart failure was low. Patients with less accurate recognition of their comorbidities may be at higher risk for a composite of all‐cause mortality or heart failure rehospitalization.

Abstract Although postural hypotension (PH) is reportedly associated with mortality in the general population, the prognostic value for heart failure is unclear. This was a post-hoc analysis of FRAGILE-HF, a prospective multicenter observational study focusing on frailty in elderly patients with heart failure. Overall, 730 patients aged ≥ 65 years who were hospitalized with heart failure were enrolled. PH was defined by evaluating seated PH, and was defined as a fall of ≥ 20 mmHg in systolic and/or ≥ 10 mmHg in diastolic blood pressure within 3 min after transition from a supine to sitting position. The study endpoints were all-cause death and heart failure readmission at 1 year. Predictive variables for the presence of PH were also evaluated. PH was observed in 160 patients (21.9%). Patients with PH were more likely than those without PH to be male with a New York Heart Association classification of III/IV. Logistic regression analysis showed that male sex, severe heart failure symptoms, and lack of administration of angiotensin-converting enzyme inhibitors were independently associated with PH. PH was not associated with 1-year mortality, but was associated with a lower incidence of readmission after discharge after adjustment for other covariates. In conclusion, PH was associated with reduced risk of heart failure readmission but not with 1-year mortality in older patients with heart failure.

Abstract Aims White blood cell (WBC) count in healthy people is associated with the risk of coronary artery disease (CAD) and mortality. This study aimed to determine whether WBC count predicts heart failure (HF) requiring hospitalization as well as all‐cause death, acute myocardial infarction (AMI) and stroke in patients with Type 2 diabetes mellitus and established CAD. Methods We conducted this retrospective registry study that enrolled consecutive patients with Type 2 diabetes mellitus and CAD based on coronary arteriography records and medical charts at 70 teaching hospitals in Japan from 2005 to 2015. A total of 7608 participants (28.2% women, mean age 68 ± 10 years) were eligible. In the cohort, the median (interquartile range) and mean follow‐up durations were 39 (16.5–66.1 months) and 44.3 ± 32.7 months, respectively. The primary outcome was HF requiring hospitalization. The secondary outcomes were AMI, stroke, all‐cause death, 3‐point major adverse cardiovascular events (MACE) (AMI/stroke/death) and 4‐point MACE (AMI/stroke/death/HF requiring hospitalization). Outcomes were reported as cumulative incidences (proportion of patients experiencing an event) and incidence rates (events/100 person‐years). The primary and secondary outcomes were assessed using the Kaplan–Meier method and were compared using the log‐rank test stratified by the baseline WBC count. The association between the WBC count at baseline and each MACE was assessed using the Cox proportional hazard model and expressed as the hazard ratio (HR) and 95% confidence interval (CI) after adjusting for other well‐known risk factors for MACE. Results During the follow‐up, 880 patients were hospitalized owing to HF. The WBC Quartile 4 (≥7700 cells/μL) had significantly lower HF event‐free survival rate (log‐rank test, P

Abstract Aims Although aging is strongly associated with both heart failure and a decline in gait speed, a definition of slowness incorporating an age‐related decline has yet to be developed. We aimed to define an event‐driven cut‐off for the relative decline in gait speed against age‐adjusted reference values derived from the general population and evaluate its prognostic implications. Methods and results Standardized gait speed (SGS) was defined as the median gait speed stratified by age, sex, and height in 3777 elderly (age ≥ 65 years) individuals without a history of cardiovascular diseases (Tokyo Metropolitan Institute of Gerontology‐Longitudinal Interdisciplinary Study on Aging: general population cohort). The mortality event‐driven optimal cut‐off of the SGS ratio (actual gait speed divided by the respective SGS) was defined using FRAGILE‐HF cohort data and externally validated using Kitasato cohort data, comprising 1301 and 1247 hospitalized elderly patients with heart failure, respectively. Using FRAGILE‐HF data, the optimal SGS ratio cut‐off was determined as 0.527. In the Kitasato cohort, SGS ratio

Abstract Frailty is a common comorbidity associated with adverse events in patients with heart failure, and early recognition is key to improving its management. We hypothesized that the AST to ALT ratio (AAR) could be a marker of frailty in patients with heart failure. Data from the FRAGILE-HF study were analyzed. A total of 1327 patients aged ≥ 65 years hospitalized with heart failure were categorized into three groups based on their AAR at discharge: low AAR (AAR

Abstract Aims There have been no investigations of the prevalence and clinical implications of coexistence of anaemia and frailty in older patients hospitalized with heart failure (HF) despite their association with adverse health outcomes. The present study was performed to determine the prevalence and prognostic value of the coexistence of anaemia and frailty in hospitalized older patients with HF. Methods and results We performed post hoc analysis of consecutive hospitalized HF patients ≥65 years old enrolled in the FRAGILE‐HF, which was the prospective, multicentre, observational study. Anaemia was defined as haemoglobin

Abstract Percutaneous coronary intervention (PCI) is sometimes considered as an alternative therapeutic strategy to surgical revascularization in patients with coronary artery disease (CAD) and reduced left ventricular ejection fraction (LVEF). However, the types or conditions of patients that receive the clinical benefit of left ventricular reverse remodelling (LVRR) remain unknown. The purpose of this study was to investigate the determinants of LVRR following PCI in CAD patients with reduced LVEF. From 4394 consecutive patients who underwent PCI, a total of 286 patients with reduced LV systolic function (LVEF

BackgroundObstructive sleep apnea (OSA) is a potential risk factor in cardiovascular diseases, including arrhythmia, coronary artery disease, and heart failure (HF). Continuous positive airway pressure (CPAP) therapy is an effective therapy for OSA and the underlying HF, partly through a 5–9% increase in the left ventricular ejection fraction (LVEF). However, the data on the factors associated with the efficacy of CPAP on LVEF in patients with HF complicated by OSA are scarce. This study aimed to investigate whether LVEF improves in patients with OSA and HF after 1 month of CPAP therapy, and to clarify which factors are associated with the degree of LVEF improvement.MethodThis was a prospective, single-arm, open-label study. We enrolled moderate-to-severe patients with OSA and HF who were being followed up at the cardiovascular center of Toranomon Hospital (Tokyo, Japan). The parameters of sleep study and LVEF were assessed at the baseline and after 1 month of CPAP. The multivariate regression analyses, with changes in LVEF as a dependent variable, were performed to determine the factors that were associated with the degree of LVEF improvement.ResultsWe analyzed 55 consecutive patients with OSA and HF (mean age: 60.7 ± 12.2 years, mean LVEF value: 37.2 ± 9.8%). One month of CPAP treatment decreased the apnea-hypopnea index (AHI) from 45.3 ± 16.1 to 5.4 ± 4.1 per hour, and the LVEF improved from 37.2 ± 9.8 to 43.2 ± 11.7%. The multivariate regression analyses demonstrated that age and body mass index (BMI) were significant determinants of LVEF improvement.ConclusionThe LVEF improved significantly after 1 month of CPAP therapy in Japanese patients with OSA and HF. Multivariate regression analyses indicated that an improvement in LVEF was likely to be observed in young patients with obesity.

Abstract Vascular toxicity is one of serious complications following cisplatin‐based chemotherapy. This case suggests that cisplatin has a potential risk of delayed occurrence of vasospastic angina. It is important to perform careful history taking including discontinued drugs for differential diagnosis of chest pain.

Background Frailty is conceptualized as an accumulation of deficits in multiple areas and is strongly associated with the prognosis of heart failure (HF). However, the social domain of frailty is less well investigated. We prospectively evaluated the clinical characteristics and prognostic impact of social frailty (SF) in elderly patients with HF. Methods and Results FRAGILE‐HF (prevalence and prognostic value of physical and social frailty in geriatric patients hospitalized for heart failure) is a multicenter, prospective cohort study focusing on patients hospitalized for HF and aged ≥65 years. We defined SF by Makizako’s 5 items, which have been validated as associated with future disability. The primary end point was a composite of all‐cause death and rehospitalization because of HF. The impact of SF on all‐cause mortality alone was also evaluated. Among 1240 enrolled patients, 825 (66.5%) had SF. During the 1‐year observation period after discharge, the rates of the combined end point and all‐cause mortality were significantly higher in patients with SF than in those without SF (Log‐rank test: both P

Patients with advanced heart failure often experience dyspnea, fatigue, edema, and appetite loss. If these symptoms are refractory to treatment, palliative care via a team approach is necessary. We describe a patient with stage D heart failure whose dyspnea and overall condition improved with comprehensive medical treatments including conventional medications for heart failure, continuous infusions of catecholamine and diuretic, and oral hydromorphone. A 67-year-old man with a 12-year history of dilated cardiomyopathy was admitted to our hospital due to exacerbation of heart failure. Despite continuous infusion of catecholamine and diuretic, his dyspnea and liver and renal function continued to worsen. Oral hydromorphone was administered to relieve his refractory dyspnea, which also improved his conditions, continuous infusion of the catecholamine and diuretic could withdraw. Oral low-dose hydromorphone used in the present case might be a helpful agent for treating dyspnea in stage D heart failure patients with renal dysfunction.

Abstract Background Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited myocardial disease characterized by fibrofatty replacement and ventricular arrhythmias. ARVC is believed to be a disease of the young, with most cases being diagnosed before the age of 40 years. We report here a case of newly diagnosed ARVC in an octogenarian associated with a pathogenic variant in the plakophilin 2 gene (PKP2). Case presentation An 80-year-old Japanese man was referred for sustained ventricular tachycardia. His baseline electrocardiogram showed negative T waves in V1–V4. Right ventriculography showed right ventricular aneurysm. Because this case met three major criteria, ARVC was diagnosed. He was successfully treated with radiofrequency ablation and oral amiodarone. Genetic analysis identified an insertion mutation in exon 8 of PKP2 (1725_1728dupGATG), which caused a frameshift and premature termination of translation (R577DfsX5). Conclusions To the best of our knowledge, this is the first report of newly diagnosed ARVC in an octogenarian associated with a loss-of-function PKP2 pathogenic variant. Although the late clinical presentation of ARVC is rare, it should be included in the differential diagnosis when treating older patients with ventricular tachyarrhythmias.

BackgroundThe prognostic implications of combined pre- and post-capillary pulmonary hypertension (Cpc-PH) in patients with pulmonary hypertension due to left heart disease (PH-LHD) remain controversial. The aim of this retrospective study was to evaluate the new PH-LHD criteria, recommended by the 6th World Symposium on Pulmonary Hypertension and to determine the prognostic value of Cpc-PH.MethodsA total of 701 patients with symptomatic heart failure who had undergone right-heart catheterization were divided into the following four groups: (i) Isolated post-capillary PH (Ipc-PH) group; mean pulmonary artery pressure (mPAP) >20 mmHg, pulmonary artery wedge pressure (PAWP) >15 mmHg, and pulmonary vascular resistance (PVR) 20 mmHg, PAWP >15 mmHg, and PVR ≥3 WU (iii) borderline-PH group; mPAP >20 mmHg and PAWP ≤15 mmHg (iv) non-PH group; mPAP ≤20 mmHg. Multivariate Cox hazard analysis was used to investigate whether Cpc-PH was associated with cardiac outcomes.ResultsThe study subjects were allocated into the Ipc-PH (n = 268), Cpc-PH (n = 54), borderline-PH (n = 112), or non-PH (n = 267) groups. The Cpc-PH group was associated significantly with adverse cardiac events even after adjustment for clinically relevant confounding factors for heart failure prognosis (vs. non-PH group: HR 2.98 [95% CI 1.81-4.90], P ConclusionsThe new definitions of PH-LHD stratified patients into 4 categories. Long-term clinical outcomes were significantly different between the four categories, with Cpc-PH having the worst cardiac outcomes.

BACKGROUND:Since the long fluoroscopy time in primary PCI for ST-segment elevation myocardial infarction (STEMI) could be an indicator of delayed reperfusion, it should be important to recognize which types of lesions require longer fluoroscopy-time in primary PCI. The purpose of this study was to investigate the association of the long fluoroscopy-time with clinical factors in primary percutaneous coronary interventions (PCI). METHODS:A total of 539 patients who underwent primary PCI were divided into the conventional fluoroscopy-time group (Q1-Q4: n = 434) and the long fluoroscopy-time group (Q5: n = 105) according to the quintile of the total fluoroscopy time in primary PCI. Univariate and multivariate logistic regression analyses were performed to find associations between clinical variables and the long fluoroscopy-time. RESULTS:In univariate logistic regression analysis, prevalence of diabetes mellitus, hemodialysis, and previous CABG were significantly associated with the long fluoroscopy-time. In addition, complex lesion characteristics such as lesion length, lesion angle, tortuosity, and calcification were associated with the long fluoroscopy-time. In multivariable logistic regression analysis, lesion length [per 10 mm incremental: odds ratio (OR) 1.751, 95% confidence interval (CI) 1.397-2.195, P

BackgroundRecently, the importance of chronic total occlusion (CTO)-percutaneous coronary intervention (PCI) has been emphasized with greater success rates. In the antegrade wire based approach, it is generally considered that the guidewire would not advance from the subintimal space to the intimal space without dissection re-entry device. However, it is sometimes observed by intravascular ultrasound (IVUS) that the guidewire within the subintimal space advanced into the distal true lumen. The purpose of this study was to investigate specific conditions or characteristics which were associated with "antegrade true-sub-true" phenomenon in CTO-PCI.MethodsWe retrospectively reviewed consecutive 320 CTO lesions that underwent CTO-PCI in our institution. Among them, 16 lesions in which the IVUS confirmed the "antegrade true-sub-true" phenomenon were categorized as the true-sub-true group, whereas 27 lesions that resulted in unsuccessful CTO-PCI were categorized as the unsuccessful group. We compared the clinical, lesion, and procedural characteristics between the true-sub-true group and the unsuccessful group.ResultsThe prevalence of bifurcation with abrupt type in CTO exit-sites was significantly higher in the true-sub-true group in comparison to the unsuccessful group (75.0% vs. 25.9%, p = 0.002). The multivariate logistic regression analysis revealed that bifurcation with abrupt type in CTO exit-site (OR 8.017; 95%CI: 1.484-43.304; p = 0.016) was independent predictor of the antegrade true-sub-true phenomenon.ConclusionsIn CTO-PCI, the antegrade true-sub-true phenomenon is rare, but can be a last chance for successful PCI. Bifurcation with abrupt type in CTO exit-site was significantly associated with the antegrade true-sub-true phenomenon.

ObjectivesThis study aimed to compare the mid-term clinical outcomes of intravascular ultrasound (IVUS)-calcified nodules between percutaneous coronary intervention (PCI) with and without rotational atherectomy (RA).BackgroundThere has been a debate whether to use RA for the revascularization of calcified nodule. Although RA can ablate the calcified structure within calcified nodule and may facilitate adequate stent expansion, RA may provoke severe coronary perforation, because calcified nodule typically shows eccentric calcification.MethodsWe included 204 lesions with IVUS-calcified nodule, and divided into 73 lesions treated with RA (RA group) and 131 lesions without RA (non-RA group). After propensity-score matching, 42 lesions with RA (matched RA group) and 42 lesions without RA (matched non-RA group) were selected. We compared the clinical characteristics and outcomes between the 2 groups before and after propensity-score matching. The primary endpoint was ischemia-driven target vessel revascularization (TVR) within 1 year.ResultsAcute lumen area gain on IVUS was comparable between the matched RA group and matched non-RA group (3.9 ± 2.1 mm2 vs. 3.4 ± 1.6 mm2, p = 0.18). The stent malapposition at calcified nodules was frequently observed in both groups. The ischemia-driven TVR was not different between the 2 groups before (p = 0.82) and after propensity score-matching (p = 0.87).ConclusionsThe use of RA could not reduce the incidence of ischemia-driven TVR in lesions with IVUS-calcified nodule. Our results do not support the routine use of RA for lesions with IVUS-calcified nodule.

Abstract A 62‐year‐old man with Brugada syndrome underwent subcutaneous implantable cardioverter defibrillator implantation. The lead was positioned along the left sternal border and defibrillation threshold (DFT) testing was performed. However, ventricular fibrillation (VF) was not terminated with 65 J and 80 J shocks. Shock impedance was 82 ohms. We repositioned the lead to the right sternal border and performed DFT testing again, followed by the VF termination with a 65 J shock. Shock impedance was 59 ohms. The positional relationship among the lead, generator, and heart was changed by lead repositioning, which may have contributed to improved shock impedance and DFT.

A 74-year-old woman who developed atrial tachycardia following the Cox-Maze IV procedure underwent catheter ablation. The reentrant circuit included the coronary sinus (CS), Marshall bundle (MB), distal MB-left atrial (LA) connection, and anterolateral mitral annulus. The distal MB-LA connection was the last barrier in the conduction pathway between the CS and the left atrium. Keywords: Atrial tachycardia, Catheter ablation, Coronary sinus, Left atrial appendage, Marshall bundle

Abstract Background Saturated fatty acids have been shown to cause insulin resistance and low-grade chronic inflammation, whereas unsaturated fatty acids suppress inflammation via G-protein coupled receptor 120 (GPR120) in macrophages. However, the anti-inflammatory effects of unsaturated fatty acids in adipocytes have yet to be elucidated. Hence, the aims of the present study were to evaluate the anti-inflammatory effects of eicosapentaenoic acid (EPA) via GPR120 in adipocytes. Methods We used 250 μM palmitate as a representative saturated fatty acid. 3T3-L1 adipocytes were used for in vitro studies. We further evaluated the effect of EPA supplementation in a high-fat/high-sucrose (HFHS) diet-induced adipose tissue inflammatory mouse model. Results EPA attenuated palmitate-induced increases in inflammatory gene expression and NF-κB phosphorylation in 3T3-L1 adipocytes. Silencing of GPR120 abolished the anti-inflammatory effects of EPA. In GPR120 downstream signal analysis, EPA was found to decrease palmitate-induced increases in TAK1/TAB1 complex expression. EPA supplementation suppressed HFHS-induced crown-like structure formation in epididymal adipose tissue and altered macrophage phenotypes from M1 to M2 in the stromal vascular fraction. Moreover, the EPA-containing diet attenuated increases in adipose p-JNK and phospho-p65 NF-κB levels. Conclusions In conclusion, the findings of the present study demonstrate that EPA suppresses palmitate-induced inflammation via GPR120 by inhibiting the TAK1/TAB1 interaction in adipocytes. EPA supplementation reduced HFHS diet-induced inflammatory changes in mouse adipose tissues. These results demonstrate adipose GPR120 as a potential therapeutic target for decreasing inflammation.

BackgroundThe incidence of severe complications such as burr entrapment or perforation is considerable with rotational atherectomy (RA). Halfway RA is a novel strategy, in which an operator does not advance the burr to the end of a continuous calcified lesion, and performs balloon dilatation to treat the remaining part of the calcified lesion. The purpose of this study was to compare complications after halfway and conventional RA.MethodsWe included 307 consecutive lesions that were divided into a conventional RA group (n = 244) and halfway RA group (n = 63). In analysis 1, the incidence of complications was compared between the conventional RA and halfway RA groups. Propensity-score matching was used to match the intentional halfway RA and conventional RA. In analysis 2, the incidence of complications was compared between the matched conventional RA and intentional halfway RA groups.ResultsBurr entrapment (0.4%) and major perforation (0.8%) were observed in the conventional RA group, whereas there was no burr entrapment or perforation in the halfway RA group. The success rate of halfway RA was 90.5%, which required switching from halfway RA to conventional RA. The incidences of slow flow and periprocedural myocardial infarction with slow flow were similar between the intentional halfway RA and matched conventional RA groups.ConclusionsThere was no burr entrapment or vessel perforation following halfway RA. The incidences of slow flow and periprocedural myocardial infarction were similar between the intentional halfway RA and the matched conventional RA, indicating the safety of halfway RA.

Background: Cardiac resynchronization therapy is an effective device therapy for heart failure patients with conduction block. However, a problem with this invasive technique is the nearly 30% of non-responders. A number of studies have reported a functional line of block of cardiac excitation propagation in responders. However, this can only be detected using non-contact endocardial mapping. Further, although the line of block is considered a sign of responders to therapy, the mechanism remains unclear.Methods: Herein, we created two patient-specific heart models with conduction block and simulated the propagation of excitation based on a cellmodel of electrophysiology. In one model with a relatively narrow QRS width (176 ms), we modeled the Purkinje network using a thin endocardial layer with rapid conduction. To reproduce a wider QRS complex (200 ms) in the second model, we eliminated the Purkinje network, and we simulated the endocardial mapping by solving the inverse problem according to the actual mapping system.Results: We successfully observed the line of block using non-contact mapping in the model without the rapid propagation of excitation through the Purkinje network, although the excitation in the wall propagated smoothly. This model of slow conduction also reproduced the characteristic properties of the line of block, including dense isochronal lines and fractionated local electrocardiograms. Further, simulation of ventricular pacing from the lateral wall shifted the location of the line of block. By contrast, in the model with the Purkinje network, propagation of excitation in the endocardial map faithfully followed the actual propagation in the wall, without showing the line of block. Finally, switching the mode of propagation between the two models completely reversed these findings.Conclusions: Our simulation data suggest that the absence of rapid propagation of excitation through the Purkinje network is the major cause of the functional line of block recorded by non-contact endocardial mapping. The line of block can be used to identify responders as these patients loose rapid propagation through the Purkinje network.

Abstract Erythropoietin (EPO), a type I cytokine originally identified for its critical role in hematopoiesis, has been shown to have non-hematopoietic, tissue-protective effects, including suppression of atherosclerosis. However, prothrombotic effects of EPO hinder its potential clinical use in nonanemic patients. In the present study, we investigated the antiatherosclerotic effects of helix B surface peptide (HBSP), a nonerythropoietic, tissue-protective compound derived from EPO, by using human umbilical vein endothelial cells (HUVECs) and human monocytic THP-1 cells in vitro and Watanabe heritable hyperlipidemic spontaneous myocardial infarction (WHHLMI) rabbits in vivo. In HUVECs, HBSP inhibited apoptosis (≈70%) induced by C-reactive protein (CRP), a direct mediator of atherosclerosis. By using a small interfering RNA approach, Akt was shown to be a key molecule in HBSP-mediated prevention of apoptosis. HBSP also attenuated CRP-induced production of tumor necrosis factor (TNF)-α and matrix metalloproteinase-9 in THP-1 cells. In the WHHLMI rabbit, HBSP significantly suppressed progression of coronary atherosclerotic lesions as assessed by mean cross-sectional stenosis (HBSP 21.3 ± 2.2% versus control peptide 38.0 ± 2.7%) and inhibited coronary artery endothelial cell apoptosis with increased activation of Akt. Furthermore, TNF-α expression and the number of M1 macrophages and M1/M2 macrophage ratio in coronary atherosclerotic lesions were markedly reduced in HBSP-treated animals. In conclusion, these data demonstrate that HBSP suppresses coronary atherosclerosis, in part by inhibiting endothelial cell apoptosis through activation of Akt and in association with decreased TNF-α production and modified macrophage polarization in coronary atherosclerotic lesions. Because HBSP does not have the prothrombotic effects of EPO, our study may provide a novel therapeutic strategy that prevents progression of coronary artery disease.