Impact of Sex Differences on Clinical Outcomes in Patients Following Primary Revascularization for Acute Myocardial Infarction　- Insights From the Japanese Nationwide Registry.

BACKGROUND: Women with acute myocardial infarction (AMI) often present a worse risk profile and experience a higher rate of in-hospital mortality than men. However, sex differences in post-discharge prognoses remain inadequately investigated. We examined the impact of sex on 1-year post-discharge outcomes in patients with AMI undergoing percutaneous coronary intervention.Methods and Results: We extracted patient-level data for the period January 2017-December 2018 from the J-PCI OUTCOME Registry, endorsed by the Japanese Association of Cardiovascular Intervention and Therapeutics. One-year all-cause and cardiovascular mortality and major adverse cardiovascular events were compared between men and women. In all, 29,856 AMI patients were studied, with 6,996 (23.4%) being women. Women were significantly older and had a higher prevalence of comorbidities than men. Crude all-cause mortality was significantly higher among women than men (7.5% vs. 5.4% [P<0.001] for ST-elevation myocardial infarction [STEMI]; 7.0% vs. 5.2% [P=0.006] for non-STEMI). These sex-related differences in post-discharge outcomes were attenuated after stratification by age. Multivariate analysis demonstrated an increase in all-cause mortality in both sexes with increasing age and advanced-stage chronic kidney disease (CKD). CONCLUSIONS: Within this nationwide cohort, women had worse clinical outcomes following AMI than men. However, these sex-related differences in outcomes diminished after adjusting for age. In addition, CKD was significantly associated with all-cause mortality in both sexes.

Early Detection and Prediction of Anthracycline-Induced Cardiotoxicity　- A Prospective Cohort Study.

BACKGROUND: In the present study, we aimed to investigate whether early cardiac biomarker alterations and echocardiographic parameters, including left atrial (LA) strain, can predict anthracycline-induced cardiotoxicity (AIC) and thus develop a predictive risk score.Methods and Results: The AIC registry is a prospective, observational cohort study designed to gather serial echocardiographic and biomarker data before and after anthracycline chemotherapy. Cardiotoxicity was defined as a reduction in left ventricular ejection fraction (LVEF) ≥10 percentage points from baseline and <55%. In total, 383 patients (93% women; median age, 57 [46-66] years) completed the 2-year follow-up; 42 (11.0%) patients developed cardiotoxicity (median time to onset, 292 [175-440] days). Increases in cardiac troponin T (TnT) and B-type natriuretic peptide (BNP) and relative reductions in the left ventricular global longitudinal strain (LV GLS) and LA reservoir strain [LASr] at 3 months after anthracycline administration were independently associated with subsequent cardiotoxicity. A risk score containing 2 clinical variables (smoking and prior cardiovascular disease), 2 cardiac biomarkers at 3 months (TnT ≥0.019 ng/mL and BNP ≥31.1 pg/mL), 2 echocardiographic variables at 3 months (relative declines in LV GLS [≥6.5%], and LASr [≥7.5%]) was generated. CONCLUSIONS: Early decline in LASr was independently associated with subsequent cardiotoxicity. The AIC risk score may provide useful prognostication in patients receiving anthracyclines.

Balloon surface temperature-controlled ablation using a second-generation radiofrequency HotBalloon: an in vivo feasibility study.

AIMS: The first-generation radiofrequency HotBalloon (RHB) is a size-adjustable single-shot device used in atrial fibrillation. The energy output is determined by its central temperature and not by its balloon surface temperature (BST), thus limiting its efficacy and safety. Therefore, a second-generation RHB was developed to monitor BST and enable BST-controlled ablation. This animal study aims to evaluate the accuracy of a newly developed BST-monitoring system and validate the optimal BST for ablation. METHODS AND RESULTS: In Protocol 1, thermocapsules were attached to the superior vena cava (SVC) epicardium. The accuracy of BST monitoring was examined during SVC isolation. In Protocol 2, the efficacy and safety of different BST-controlled ablations were examined. In the acute model, electrophysiological and pathological findings were assessed after energy applications with BST at 51, 54, 57, and 60°C. In the chronic model, the lesion durability and pathological findings were assessed 8 weeks after BST-controlled ablation (57 and 60°C). A significant positive correlation was found between the epicardial temperature and the BST-monitoring value (r = 0.98). In the acute model, all target veins were electrically isolated with BST-controlled ablation at ≥57°C (18/18, 100%). In the chronic model, durable lesions were observed in all veins at 60°C, while 44% of the veins showed reconnection at 57°C. In both pathological analyses, significantly greater lesions were observed at 60°C than at 57°C. There were no significant differences in adverse events between the two groups. CONCLUSION: Balloon surface temperature-controlled ablation at 60°C using the second-generation RHB may be optimal for creating durable lesions without compromising safety.

Trends in Unplanned Admissions of Patients With Adult Congenital Heart Disease Based on the Japanese Registry of All Cardiac and Vascular Diseases-Diagnosis Procedure Combination Study.

BACKGROUND: The prevalence of adult congenital heart disease (ACHD) is increasing rapidly and in particular, patients who underwent complicated surgeries are reaching their youth and middle age. Therefore, the need for ACHD treatment will increase, but the current medical situation is unknown. In this study we assessed trends in unplanned admissions in patients with ACHD in Japan.Methods and Results: From the Japanese Registry of All Cardiac and Vascular Diseases-Diagnosis Procedure Combination, a nationwide claim-based database, we selected patients aged >15 years with CHD defined by the International Classification of Diseases, 10th Revision codes. We identified 39,676 admissions between April 2012 and March 2018; 10,444 (26.3%) were unplanned. Main diagnoses were categorized into 3 degrees of complexity (severe, moderate, and mild) and other. Among unplanned admissions, the proportion of the severe group increased with time. Patients in the mild group were significantly older than those in the moderate and severe groups (median age: 70.0, 39.0, and 32.0 years, respectively). There were 765 deaths during hospitalization (overall mortality rate, 7.3%). The odds ratio of death during admission was significantly higher in patients aged >50 years, especially in the moderate group. CONCLUSIONS: Patients with moderate or severe ACHD tended to experience unplanned admissions at a younger age. In anticipation of greater numbers of new, severe patients, we need to prepare for their increasing medical demands.

Efficacy of Low-Dose Isoproterenol Infusion for the Exclusion of a Left Atrial Appendage Thrombus in Patients With Dense Spontaneous Echo Contrast Caused by Atrial Fibrillation.

BACKGROUND: In patients with atrial fibrillation (AF) and severe blood stasis in the left atrial appendage (LAA), dense spontaneous echo contrast (SEC) disturbs the distinct visualization of the LAA interior, thus making thrombus diagnosis inconclusive. We aimed to prospectively assess the efficacy and safety of a protocol for a low-dose isoproterenol (ISP) infusion to reduce SEC to exclude an LAA thrombus.Methods and Results: We enrolled 17 patients with AF and dense SEC (Grade 4 or sludge). ISP was infused with gradually increasing doses of 0.01, 0.02, and 0.03 µg/kg/min at 3-min intervals. After increasing the dose to 0.03 µg/kg/min for 3 min, or when the LAA interior was visible, the infusion was terminated. We reassessed the SEC grade, presence of an LAA thrombus, LAA function, and left ventricular ejection fraction (LVEF) within 1 min of ISP termination. Compared with baseline, ISP significantly increased LAA flow velocity, the LAA emptying fraction, LAA wall velocities, and LVEF (all P<0.01). ISP administration significantly reduced the SEC grade (median) from 4 to 1 (P<0.001). The SEC grade decreased to ≤2 in 15 (88%) patients, and the LAA thrombus was excluded. There were no adverse events. CONCLUSIONS: Low-dose ISP infusion may be effective and safe to reduce SEC and exclude an LAA thrombus by improving LAA function and LVEF.

In-Hospital Death and End-of-Life Status Among Patients With Adult Congenital Heart Disease　- A Retrospective Study Using the JROAD-DPC Database in Japan.

BACKGROUND: The end-of-life (EOL) status, including age at death and treatment details, of patients with adult congenital heart disease (ACHD) remains unclear. This study investigated the EOL status of patients with ACHD using a nationwide Japanese database.Methods and Results: Data on the last hospitalization of 26,438 patients with ACHD aged ≥15 years, admitted between 2013 and 2017, were included. Disease complexity (simple, moderate, or great) was classified using International Classification of Diseases, 10th Revision codes. Of the 853 deaths, 831 patients with classifiable disease complexity were evaluated for EOL status. The median age at death of patients in the simple, moderate, and great disease complexity groups was 77.0, 66.5, and 39.0 years , respectively. The treatments administered before death to patients in the simple, moderate, and great complexity groups included cardiopulmonary resuscitation (30.1%, 35.7%, and 41.9%, respectively), percutaneous cardiopulmonary support (7.2%, 16.5%, and 16.3%, respectively), and mechanical ventilation (58.7%, 72.2%, and 75.6%, respectively). Overall, 70% of patients died outside of specialized facilities, with >25% dying after ≥31 days of hospitalization. CONCLUSIONS: Nationwide data showed that patients with ACHD with greater disease complexity died at a younger age and underwent more invasive treatments before death, with many dying after ≥1 month of hospitalization. Discussing EOL options with patients at the appropriate time is important, particularly for patients with greater disease complexity.

Long-QT Syndrome with Peripartum Cardiomyopathy Causing Fatal Ventricular Arrhythmia after Delivery.

Although rare, long QT syndrome (LQTS) and peripartum cardiomyopathy (PPCM) are the major causes of maternal cardiovascular death. We herein present a case study of a 23-year-old woman with LQTS, pregnancy-induced hypertension, and PPCM. During the postpartum period, her left ventricular systolic function had severely decreased, requiring the administration of loop diuretics. Diuretics cause several changes in the circulating blood volume, electrolyte balance, and hormonal status during pregnancy, delivery, and the peripartum period. Extreme QTc prolongation and fatal ventricular arrhythmia require frequent defibrillation. For the patient in this study, we corrected her electrolyte abnormality, and eventually, we controlled the arrhythmia by administering a ß-blocker and Na-channel blocker. Although the arrhythmia subsided, she continued on medication after discharge to prevent the recurrence of fatal arrhythmia. In conclusion, close attention should be paid to patients with LQTS, especially when some changes that may lead to QTc prolongation could occur during the peripartum period.

Longitudinal Changes in Natriuretic Peptides and Reverse Cardiac Remodeling in Patients with Heart Failure Treated with Sacubitril/Valsartan Across the Left Ventricular Ejection Traction Spectrum.

Sacubitril/valsartan improves outcomes in patients with heart failure (HF) with reduced ejection fraction. However, the relationship between longitudinal changes in natriuretic peptides and echocardiographic parameters in patients with HF treated with sacubitril/valsartan across the left ventricular ejection fraction (LVEF) range is not fully understood.In patients with HF treated with sacubitril/valsartan, comprehensive data on natriuretic peptides, including atrial natriuretic peptide (ANP), N-terminal pro-brain-type natriuretic peptide (NT-proBNP), BNP, and echocardiography, were measured after 6 months of treatment. We assessed the change in natriuretic peptides and echocardiographic parameters in LVEF classification subgroups.Among 49 patients, the median ANP concentration increased from 55 pg/mL at baseline to 78 pg/mL (P < 0.001). The NT-proBNP concentration decreased from 250 pg/mL to 146 pg/mL (P < 0.001). No significant change was observed in the BNP concentration (P = 0.640). The trajectories of each natriuretic peptide in patients with LVEF > 40% (n = 22) were similar to those in individuals with LVEF ≤ 40% (n = 27). Regardless of LVEF classification, echocardiography at 6 months showed a significant improvement in LVEF, left ventricular end-diastolic volume, and the ratio of early diastolic mitral inflow velocity to early diastolic mitral annulus velocity (E/e'). The reduction in natriuretic peptide concentration was related to LV reverse remodeling and decreased left and right atrial pressures assessed by E/e' and inferior vena cava diameter.Sacubitril/valsartan induced an increase in ANP, a reduction in NT-proBNP, and no change in plasma BNP, regardless of LVEF. It caused LV reverse remodeling, and the natriuretic peptide concentration changes were associated with structural and functional echocardiographic parameters.

Clinical Characteristics of Non-Valvular Atrial Fibrillation Patients With a Large Left Atrial Appendage Ostium-Limiting Percutaneous Closure.

BACKGROUND: The left atrial appendage (LAA) is a therapeutic target for preventing cardioembolic stroke in patients with non-valvular atrial fibrillation (NVAF). A large LAA ostium limits percutaneous LAA closure. This study investigated the characteristics and factors associated with a large LAA ostium in Japanese patients with NVAF.Methods and Results: In 1,102 NVAF patients, the maximum LAA diameter was measured using transesophageal echocardiography (TEE). A large LAA ostium was defined by a maximum diameter of >30 mm. Forty-four participants underwent repeated TEEs, and changes in LAA size under lasting AF were assessed. A large LAA ostium was observed in 3.1% of all participants and 8.9% of patients with long-standing persistent AF (LSAF). The large LAA group had greater CHA2DS2-VASc (P=0.024) and HAS-BLED scores (P=0.046) and a higher prevalence of LAA thrombus (P=0.004) than did the normal LAA group. LSAF, moderate or severe mitral regurgitation, left atrial volume ≥42 mL/m2, E/E' ratio ≥9.5, and left ventricular mass ≥85 mg/m2were independently associated with a large LAA ostium (P<0.001, P<0.001, P=0.009, P=0.009, and P=0.032, respectively). In 44 patients with lasting AF, the LAA ostial diameter increased over time (P<0.001). CONCLUSIONS: NVAF patients with a large LAA ostium may have a higher risk of stroke and bleeding. LSAF and factors leading to LA overload may be closely associated with LAA ostial dilatation and can promote it.

Sodium Glucose Co-Transporter 2 Inhibitors Improve Renal Congestion and Left Ventricular Fibrosis in Rats With Hypertensive Heart Failure.

BACKGROUND: Elevated central venous pressure (CVP) in heart failure causes renal congestion, which deteriorates prognosis. Sodium glucose co-transporter 2 inhibitor (SGLT2-i) improves kidney function and heart failure prognosis; however, it is unknown whether they affect renal congestion. This study investigated the effect of SGLT2-i on the kidney and left ventricle using model rats with hypertensive heart failure.Methods and Results: Eight rats were fed a 0.3% low-salt diet (n=7), and 24 rats were fed an 8% high-salt diet, and they were divided into 3 groups of untreated (n=6), SGLT2-i (canagliflozin; n=6), and loop diuretic (furosemide; n=5) groups after 11 weeks of age. At 18 weeks of age, CVP and renal intramedullary pressure (RMP) were monitored directly by catheterization. We performed contrast-enhanced ultrasonography to evaluate intrarenal perfusion. In all high-salt fed groups, systolic blood pressure was elevated (P=0.287). The left ventricular ejection fraction did not differ among high-salt groups. Although CVP decreased in both the furosemide (P=0.032) and the canagliflozin groups (P=0.030), RMP reduction (P=0.003) and preserved renal medulla perfusion were only observed in the canagliflozin group (P=0.001). Histological analysis showed less cast formation in the intrarenal tubule (P=0.032), left ventricle fibrosis (P<0.001), and myocyte thickness (P<0.001) in the canagliflozin group than in the control group. CONCLUSIONS: These results suggest that SGLT2-i causes renal decongestion and prevents left ventricular hypertrophy, fibrosis, and dysfunction.

Effect of Novel Stratified Lipid Risk by "LDL-Window" and Flow-Mediated Dilation on the Prognosis of Coronary Artery Disease Using the FMD-J Study A Data.

BACKGROUND: Elevated levels of triglyceride (TG) and non-high-density lipoprotein cholesterol (non-HDL-C) are regarded as a residual lipid risk in low-density lipoprotein cholesterol (LDL-C)-lowering therapy. This study investigated the association between lipid risk stratified by TG and non-HDL-C and the prognosis of patients with coronary artery disease (CAD), and the association between stratified lipid risk and flow-mediated dilatation (FMD) index.Methods and Results: The 624 CAD patients enrolled in flow-mediated dilation (FMD)-J study A were divided into 4 groups: low-risk group (n=413) with TG <150 mg/dL and non-HDL-C <170 mg/dL; hyper-TG group (n=180) with TG ≥150 mg/dL and non-HDL-C <170 mg/dL; hyper-non-HDL group (n=12) with TG <150 mg/dL and non-HDL-C ≥170 mg/dL; and high-risk group (n=19) with TG ≥150 mg/dL and non-HDL-C ≥170 mg/dL. Comparison of the groups showed the cumulative incidence of a 3-point major adverse cardiovascular event (MACE) was different and highest in the high-risk group in all the patients (P=0.009), and in patients with a FMD index ≥7.0% (P=0.021), but not in those with a FMD index <7.0%. Multivariable regression analysis showed that high lipid risk (P=0.019) and FMD <7.0% (P=0.040) were independently correlated with the incidence of a 3-point MACE. CONCLUSIONS: Novel stratification of lipid risk, simply using TG and non-HDL-C levels, combined with FMD measurement, is useful for predicting cardiovascular outcomes in patients with CAD.

Right bundle branch block and risk of cardiovascular mortality: the Ibaraki Prefectural Health Study.

Historically, a right bundle branch block has been considered a benign finding in asymptomatic individuals. However, this conclusion is based on a few old studies with small sample sizes. We examined the association between a complete right bundle branch block (CRBBB) and subsequent cardiovascular mortality in the general population in Japan. In this large community-based cohort study, data of 90,022 individuals (mean age, 58.5 ± 10.2 years; 66.2% women) who participated in annual community-based health check-ups were assessed. Subjects were followed up from 1993 to the end of 2016. Cox proportional hazards' models and log-rank tests were used for the data analysis. CRBBB was documented in 1,344 participants (1.5%). Among all included participants, CRBBB was associated with an increased risk of cardiovascular mortality after adjustment for all potential confounders (hazard ratio [HR] 1.21; 95% confidence interval [CI] 1.06-1.38). The increased risk of cardiovascular mortality was particularly evident in women aged < 65 years (HR 2.00; 95% CI 1.34-2.98) and men aged ≥ 65 years (HR 1.28; 95% CI 1.06-1.55). CRBBB is associated with an increased risk of cardiovascular mortality in women aged < 65 years and men aged ≥ 65 years. Clinicians should be aware of the presence of CRBBB in young women and elderly men, even if they exhibit no symptoms.

Obstetric venous thromboembolism: Evaluation of prophylactic approach based on risk scores, D-dimer levels, and ultrasonography findings in a tertiary hospital in Japan.

AIM: Pulmonary embolism remains a leading cause of maternal mortality in developed countries despite developments in venous thromboembolism prophylaxis strategies. This study aimed to evaluate the effectiveness of our approach involving risk-scoring, D-dimer level assessment, and ultrasonography for obstetric venous thromboembolism. METHODS: This retrospective cohort study included women who delivered at 22-41 weeks of gestation in The University of Tsukuba Hospital, Japan between January and December 2020. Venous thromboembolism risk (determined according to Japanese guidelines) and D-dimer levels were evaluated within 20 weeks of gestation, 30-34 weeks of gestation, and during the pre-delivery period (36 weeks of gestation or any time before preterm delivery). Compression and color Doppler ultrasonography for lower extremity deep vein thrombosis were performed if D-dimer levels were ≥3.2 µg/mL (for those undergoing cesarean delivery, 1.0 µg/mL). RESULTS: Of 1026 women, 6 women had deep vein thrombosis during pregnancy and 1 during the puerperium period. Pulmonary embolism was not observed. The D-dimer screening result was positive for 8 women (2%) within 20 weeks of gestation (deep vein thrombosis was confirmed in 3 of them), 87 women (10%) (no deep vein thrombosis) at 30-34 weeks of gestation, and 367 women (36%) during the pre-delivery period (asymptomatic deep vein thrombosis in one). Based on the Japanese guidelines, 1%, 11%, 33%, and 55% of women had high, intermediate, low, and no postpartum risk factors, respectively. CONCLUSIONS: Our approach appears useful for antenatal venous thromboembolism screening in the first trimester. For postpartum prophylaxis, more cost-effective strategies are needed.

Successful surgical resection plus surgical cryoablation for the treatment of a large left ventricular fibroma.

Residual tumor mass after large cardiac fibroma resection carries long-term risk, but cryoablation is useful during surgery to remove such tissue. Here, we present a case of a large cardiac fibroma of the posterior wall of the left ventricle, discovered during long-term, episodic ventricular tachycardia. Resection with cryoablation completely removed the tumor, eliminating postoperative, distant ventricular arrhythmias.

Prognostic Value of Apical Sparing of Longitudinal Strain in Patients with Symptomatic Aortic Stenosis.

Background: Older patients with aortic stenosis (AS) have a higher incidence of wild-type transthyretin cardiac amyloidosis (ATTR-CA). This study aimed to determine whether apical sparing of longitudinal strain (LS) could help diagnose ATTR-CA and provide useful prognostic information in symptomatic AS. Methods: We performed vendor-independent two-dimensional speckle-tracking analysis of regional and global left ventricular LS in 16 patients with ATTR-CA and 31 patients with non-obstructive hypertrophic cardiomyopathy to determine the best cutoff value of the apical sparing ratio (APSR) for diagnosing ATTR-CA. We then determined the prevalence in patients who had an APSR higher than the best cutoff value and investigated its prognostic value in 230 patients with symptomatic AS. To determine the natural history of symptomatic AS, patients who had aortic valve replacement were censored at the time of surgery. Results: The best cutoff value of APSR was 0.76. APSR ≥ 0.76 was observed in 108 patients with symptomatic AS (48%). The prevalence was not different among the four AS subgroups. During a median follow-up period of 5.7 months, 47 patients had cardiac events. Cox proportional hazards analysis revealed that neither APSR nor APSR ≥ 0.76 was significantly associated with future cardiac events. Conclusions: Apical sparing was frequently observed in patients with symptomatic AS, and it was not a useful predictor of future adverse outcomes. Our results suggest that the underlying cause of apical sparing in AS may not be related to the presence of ATTR-CA.

Prognostic Impact of Changes in Intrarenal Venous Flow Pattern in Patients With Heart Failure.

BACKGROUND: It remains unclear whether intrarenal venous flow (IRVF) patterns in patients with heart failure (HF) could change over the clinical course, and whether the changes could have a clinical impact. Thus, this study aimed to clarify these characteristics as well as to identify the relation between changes in the IRVF pattern and renal impairment progression. METHODS AND RESULTS: Patients with HF with repetitive IRVF evaluations were enrolled. Doppler waveforms of IRVF were classified into the following 3 flow patterns: continuous, biphasic discontinuous, and monophasic discontinuous. Primary end points included death from cardiovascular diseases and unplanned hospitalization for HF. Finally, 108 patients with adequate images were enrolled. The IRVF in 35 patients (32.4%) shifted to another pattern at the follow-up examinations. The median brain natriuretic peptide level in the continuous flow pattern at follow-up was significantly decreased (183 to 60 pg/mL, P < .001), whereas that of the discontinuous flow pattern at follow-up was increased (from 339 to 366 pg/mL, P = .042) and the estimated glomerular filtration rate was decreased (from 55 to 50 mL/min/1.73 m2, P = .013). A multivariable Cox proportional hazard model analysis revealed that the discontinuous pattern at follow-up (P < .001) and brain natriuretic peptide (P = .021) were significantly associated with the end points, independent of age, estimated glomerular filtration rate, and serum sodium level. CONCLUSIONS: The IRVF pattern could be changed depending on the status of congestion. Persistent or worsened renal congestion, represented by discontinuous flow patterns, during the clinical courses indicated a poor prognosis accompanied by renal impairment in patients with HF.

Clinical Usefulness of the HFA-PEFF Diagnostic Scoring System in Identifying Late Elderly Heart Failure With Preserved Ejection Fraction Patients.

BACKGROUND: Diagnosis of heart failure with preserved ejection fraction (HFpEF) remains challenging in elderly. This study investigated the diagnostic ability of the HFA-PEFF scoring system in elderly patients (>75 years of age).Methods and Results:This study enrolled 286 subjects aged >75 years (130 men; mean [± SD] age 81.5±5.1 years): 95 healthy controls, 98 with hypertension (HT), and 93 with HFpEF. The HFA-PEFF score was calculated as a sum of points in functional, morphological, and biomarker domains. In the HFpEF group, 84%, 84%, and 70% of subjects met the major functional, morphological, and biomarker criteria for HFpEF, respectively. Thus, 73 subjects with HFpEF (78%) were diagnosed as having HFpEF using the HFA-PEFF scoring system. In contrast, among the healthy controls and subjects with HT, 52% and 72%, respectively, met the major functional criteria for HFpEF, 28% and 53%, respectively, met the morphological criteria, and 0% and 24%, respectively, met the biomarker criteria. As such, 32 subjects with HT (33%) were diagnosed with HFpEF. Even in the healthy control group, 72% were classified as having an intermediate probability of HFpEF, and 3 were diagnosed with HFpEF. CONCLUSIONS: In the late elderly, the HFA-PEFF scoring system diagnosed subjects with HFpEF precisely. In addition, this scoring system may be able to detect early stage HFpEF in the subclinical population.

Febuxostat does not delay progression of carotid atherosclerosis in patients with asymptomatic hyperuricemia: A randomized, controlled trial.

BACKGROUND: An elevated level of serum uric acid (SUA) is associated with an increased risk of cardiovascular disease. Pharmacological intervention with urate-lowering agents, such as the conventional purine analogue xanthine oxidase (XO) inhibitor, allopurinol, has been used widely for a long period of time in clinical practice to reduce SUA levels. Febuxostat, a novel non-purine selective inhibitor of XO, has higher potency for inhibition of XO activity and greater urate-lowering efficacy than conventional allopurinol. However, clinical evidence regarding the effects of febuxostat on atherosclerosis is lacking. The purpose of the study was to test whether treatment with febuxostat delays carotid intima-media thickness (IMT) progression in patients with asymptomatic hyperuricemia. METHODS AND FINDINGS: The study was a multicenter, prospective, randomized, open-label, blinded-endpoint clinical trial undertaken at 48 sites throughout Japan between May 2014 and August 2018. Adults with both asymptomatic hyperuricemia (SUA >7.0 mg/dL) and maximum IMT of the common carotid artery (CCA) ≥1.1 mm at screening were allocated equally using a central web system to receive either dose-titrated febuxostat (10-60 mg daily) or as a control-arm, non-pharmacological lifestyle modification for hyperuricemia, such as a healthy diet and exercise therapy. Of the 514 enrolled participants, 31 were excluded from the analysis, with the remaining 483 people (mean age 69.1 years [standard deviation 10.4 years], female 19.7%) included in the primary analysis (febuxostat group, 239; control group, 244), based on a modified intention-to-treat principal. The carotid IMT images were recorded by a single sonographer at each site and read in a treatment-blinded manner by a single analyzer at a central core laboratory. The primary endpoint was the percentage change from baseline to 24 months in mean IMT of the CCA, determined by analysis of covariance using the allocation adjustment factors (age, gender, history of type 2 diabetes, baseline SUA, and baseline maximum IMT of the CCA) as the covariates. Key secondary endpoints included changes in other carotid ultrasonographic parameters and SUA and the incidence of clinical events. The mean values (± standard deviation) of CCA-IMT were 0.825 mm ± 0.173 mm in the febuxostat group and 0.832 mm ± 0.175 mm in the control group (mean between-group difference [febuxostat - control], -0.007 mm [95% confidence interval (CI) -0.039 mm to 0.024 mm; P = 0.65]) at baseline; 0.832 mm ± 0.182 mm in the febuxostat group and 0.848 mm ± 0.176 mm in the control group (mean between-group difference, -0.016 mm [95% CI -0.051 mm to 0.019 mm; P = 0.37]) at 24 months. Compared with the control group, febuxostat had no significant effect on the primary endpoint (mean percentage change 1.2% [95% CI -0.6% to 3.0%] in the febuxostat group (n = 207) versus 1.4% [95% CI -0.5% to 3.3%] in the control group (n = 193); mean between-group difference, -0.2% [95% CI -2.3% to 1.9%; P = 0.83]). Febuxostat also had no effect on the other carotid ultrasonographic parameters. The mean baseline values of SUA were comparable between the two groups (febuxostat, 7.76 mg/dL ± 0.98 mg/dL versus control, 7.73 mg/dL ± 1.04 mg/dL; mean between-group difference, 0.03 mg/dL [95% CI -0.15 mg/dL to 0.21 mg/dL; P = 0.75]). The mean value of SUA at 24 months was significantly lower in the febuxostat group than in the control group (febuxostat, 4.66 mg/dL ± 1.27 mg/dL versus control, 7.28 mg/dL ± 1.27 mg/dL; mean between-group difference, -2.62 mg/dL [95% CI -2.86 mg/dL to -2.38 mg/dL; P < 0.001]). Episodes of gout arthritis occurred only in the control group (4 patients [1.6%]). There were three deaths in the febuxostat group and seven in the control group during follow-up. A limitation of the study was the study design, as it was not a placebo-controlled trial, had a relatively small sample size and a short intervention period, and only enrolled Japanese patients with asymptomatic hyperuricemia. CONCLUSIONS: In Japanese patients with asymptomatic hyperuricemia, 24 months of febuxostat treatment did not delay carotid atherosclerosis progression, compared with non-pharmacological care. These findings do not support the use of febuxostat for delaying carotid atherosclerosis in this population. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trial Registry UMIN000012911.

Doppler-Derived Intrarenal Venous Flow Mirrors Right-Sided Heart Hemodynamics in Patients With Cardiovascular Disease.

BACKGROUND: Interruption in Doppler intrarenal venous flow (IRVF) has been used in assessing renal congestion and in the prediction of prognosis of cardiovascular diseases. However, there is a paucity of pathophysiological knowledge, so we aimed to clarify the determinants of IRVF interruption.Methods and Results:Intrarenal Doppler studies were performed within 24 h before right-side catheterization studies. The interruption in IRVF in 73 patients was divided into a continuous pattern, and 4 discontinuous types based on the timing of interruption. Type 1, with an interruption in early systole, was associated with a-wave elevation of right atrial pressure (RAP). Type 2, with an interruption in early diastole, was associated with v-wave elevation, tricuspid regurgitation (TR), and right ventricular dysfunction. Both Type 1 and 2 were observed even in the normal range of mean RAP. Type 3, with an interruption throughout systole, was observed in advanced right heart failure patients with markedly elevated RAP, particularly elevated x-descend and atrial fibrillation. Finally, Type 4, with limited flow at systole, was observed in 2 of the patients with pulmonary arterial hypertension. CONCLUSIONS: IRVF interruption was closely related to RAP elevation at each specific point of the cardiac cycle rather than to mean RAP levels, suggesting that the characteristics of IRVF mirror right-sided heart hemodynamics, not mean RAP.

Features of Lead-Induced Tricuspid Regurgitation in Patients With Heart Failure Events After Cardiac Implantation of Electronic Devices　- A Three-Dimensional Echocardiographic Study.

BACKGROUND: Lead-induced tricuspid regurgitation (TR) after cardiac implantable electronic device (CIED) implantation is not fully understood. This study aimed to reveal the features of lead-induced TR by 3-dimensional echocardiography (3DE) in patients with heart failure (HF) events after CIED implantation.Methods and Results:In 143 patients, 3DE assessments for the tricuspid valve (TV) and right ventricular morphologies were sequentially performed within 3 days after CIED implantations, during TR exacerbations, and at ≥6 months after TR exacerbations. TR exacerbations were observed in 29 patients (median 10 months after CIED implantation, range 1-28 months), 15 of whom had lead-induced TR. In the 29 patients, the tenting height of the TV, tricuspid annular (TA) height, and TA area at baseline were independent predictors for worsening TR. In patients with lead-induced TR, tenting height of the TV and TA area were identified as the risk factors. In addition, all patients with a lead positioned on a leaflet immediately after CIED implantations developed lead-induced TR. At follow up, TR exacerbation of lead-induced TR persisted with TA remodeling, but it was improved in the lead non-related-TR group. CONCLUSIONS: TA remodeling at baseline and a lead location on a leaflet immediately after CIED implantation were associated with lead-induced TR in patients with HF events after CIED implantation. Persistent TA remodeling may make lead-induced TR refractory against HF treatments.