Prognostic impact of increase in left atrial volume following left atrial appendage closure: Insights from the OCEAN-LAAC registry.

Background: Percutaneous left atrial appendage closure (LAAC) is an effective therapy to prevent thromboembolic events among patients with atrial fibrillation (AF). However, since the left atrial appendage (LAA) contributes to left atrial volume and serves as a buffer for increasing left atrial pressure, this procedure may impair left atrium (LA) compliance, enlarge LA, and deteriorate diastolic function. In this study, we sought to investigate the change in left atrial volume index (LAVI) following LAAC and its effect on prognosis. Methods and Results: We analyzed 225 patients from the OCEAN-LAAC registry, an ongoing, multicenter Japanese study. Comparing LAVI measurements at baseline and 6 months after LAAC, no significant increase was observed (55.0 [44.0, 70.0] ml/m2 vs. 55.0 [42.0, 75.6] ml/m2; P = 0.31). However, some patients underwent LAVI increase. Particularly, a smaller LAVI (odds ratio [OR]: 0.98 [95 % confidence interval (CI): 0.97-0.996]) and elevated tricuspid regurgitation pressure (TRPG) at baseline (OR: 1.04 [95 % CI: 1.00 - 1.08]) were significantly related to the increase in LAVI at 6-month follow-up. In addition, a 5 ml/m2 increase in LAVI was significantly associated with subsequent heart failure hospitalization (HFH) (hazard ratio: 3.37 [95 % CI: 1.18-9.65]). This association, however, was not observed in patients with lower baseline LAVI (≤55 ml/m2) but was only seen in those with a baseline LAVI over 55 ml/m2. Conclusion: Our study demonstrated an increase in LAVI after LAAC was related to smaller LAVI or elevated TRPG at baseline. The LAVI increase was significantly associated with subsequent HFH.

Valuable Predictors for Non-measurability of Fractional Flow Reserve Derived From Coronary Computed Tomography Angiography.

Background The fractional flow reserve (FFR) derived from coronary computed tomography (CT) angiography (FFRCT) is a variable tool for coronary disease diagnosis that non-invasively provides the value of FFR. It can add physiological information to coronary CT angiography (CCTA) and reduce unnecessary invasive coronary angiography (CAG). However, it cannot be analyzed in some cases, which is also called "non-measurability." While FFRCT has become globally widespread, the current data on non-measurability are lacking. This study aimed to determine the rate of non-measurability and identify predictors thereof in routine clinical settings to explore potential approaches to reduce the non-measurability rate. Methods and results This retrospective observational single-center study included consecutive patients who underwent FFRCTanalysis in Japan. The mean age of the overall population was 71.3 ± 10.6, and an FFRCTof ≤0.8 was seen in 47.6% of patients with a measurable FFRCT. Of the 307 enrolled patients, FFRCT analysis was not feasible in 21 cases (6.8%). Heart rate (HR) at a CT scan and coronary calcium scores (CCS) were significantly higher in patients with non-measurability than those in patients whose FFRCT was appropriately analyzed (HR: 69.6±8.9 bpm vs. 61.0±11.1 bpm; p < 0.01; CCS; 931.2 (290.8, 1451.3) vs. 322.9 (100.7, 850.0); p < 0.01). Multiple logistic regression showed that HR was an independent predictor for non-measurability (odds ratio: 1.05; 95% confidential interval: 1.02, 1.09; p < 0.01)). Based on the receiver operating characteristic curve analysis, the optimal cut-off value of HR and CCS was 63 bpm (specificity: 67.1%; sensitivity: 76.2%) and 729.2 (specificity: 71.3%; sensitivity: 66.7%). In addition, the combination of two features (HR > 63 bpm and CCS > 729.2) showed a high negative predictive value (99.3%) for FFRCT non-measurability. Conclusions In this study, the rate of FFRCTnon-measurability was 6.8%. Higher HR at a CT scan and CCS were significantly associated with non-measurability, and in cases with both HR and CCS below a specified threshold, the likelihood of ruling out non-measurability could be significantly high. Our findings suggest that reducing the HR to ideally under 63 bpm at the time of the CT scan significantly ensures feasibility. Further study on large-scale cohorts is warranted.

Sodium-Glucose Cotransporter-2 Inhibitors in Heart Failure with Malnutrition, Frailty, Sarcopenia, or Cachexia.

(1) Background: In patients with heart failure (HF) and impaired nutritional status or decreased muscle mass, sodium-glucose cotransporter-2 inhibitors (SGLT2is) may worsen these conditions and result in poor prognosis, especially worsening of frailty. We aimed to investigate the relationship between SGLT2is and clinical outcomes, including frailty-related events, in patients with HF and malnutrition, frailty, sarcopenia, or cachexia. (2) Methods: In this retrospective observational cohort study, a global federated health research network provided data on patients with HF and malnutrition, frailty, sarcopenia, or cachexia from January 2016 to December 2021. We investigated the incidence of the composite endpoint of death or frailty-related events within one year. (3) Results: Among 214,778 patients included in the analysis, 4715 were treated with SGLT2is. After propensity score matching, 4697 patients in the SGLT2is group were matched with 4697 patients in the non-SGLT2is groups. The incidence of the composite endpoint, mortality, and frailty-related events was lower in the SGLT2is group than in the non-SGLT2is group (composite endpoint, 65.6% versus 77.6%, p < 0.001; mortality, 17.4% vs. 35.5%, p < 0.001; frailty-related events, 59.4% vs. 64.3%, p < 0.001). (4) Conclusions: Patients with HF and malnutrition, frailty, sarcopenia, or cachexia had a high incidence of death and frailty-related events. SGLT2is were associated with a lower incidence of these events.

Impact of Atrial Fibrillation Triggers on Long-Term Outcomes of a Second Catheter Ablation of Nonparoxysmal Atrial Fibrillation.

Background: Catheter ablation (CA) of atrial fibrillation (AF) triggers, including non-pulmonary vein (PV) foci, contributes to improved procedural outcomes. However, the clinical significance of an AF trigger ablation during second CA procedures for nonparoxysmal AF is unknown. Methods and Results: We enrolled 94 patients with nonparoxysmal AF undergoing a second CA. Intracardiac cardioversion during AF using high-dose isoproterenol was performed to determine the presence or absence of AF triggers. PV re-isolations were performed if PV potentials recurred, and if AF triggers appeared from any non-PV sites, additional ablation was added to those sites. We investigated the incidence of atrial arrhythmia recurrence (AAR) >3 months post-CA. Of the 94 enrolled patients, AF triggers were identified in 65 (69.1%), and of those with AF triggers, successful elimination of the triggers was achieved in 47 patients (72.3%). Multivariate analysis revealed that no observed AF triggers were a significant predictor of AAR (hazard ratio [HR] 1.97, 95% confidence interval [CI] 1.21-3.46, P=0.019). In a subanalysis of the patients with AF triggers, multivariate analysis showed that unsuccessful trigger ablation was significantly associated with AAR (HR 5.84, 95% CI 2.79-12.22, P<0.01). Conclusions: Having no observed AF triggers during a second CA session significantly increased the risk of AAR, as did unsuccessful CA of AF triggers.

Impact of Dapagliflozin on the Renal Function and Damage in Patients with Heart Failure with a Reduced Ejection Fraction.

Objective Whether or not the initial dip in the glomerular filtration rate (GFR) after the initiation of sodium-glucose co-transporter 2 inhibitors (SGLT2is) is associated with renal tubular injury in patients with heart failure with a reduced ejection fraction (HFrEF) is unclear. We therefore investigated the relationship between changes in the estimated GFR (eGFR) and urine N-acetyl-ß-D-glucosaminidase (uNAG) after the initiation of dapagliflozin in patients with HFrEF. Methods We prospectively investigated 89 patients with HFrEF who were newly started on dapagliflozin 10 mg/day. Changes in the eGFR and uNAG-to-creatinine ratio (uNAG/Cre) were evaluated at 2 weeks and 2 months after the initiation of dapagliflozin. Results The eGFR was decreased at 2 weeks but had not declined further by 2 months. The uNAG/Cre was increased at 2 weeks but had not increased further by 2 months. There was no correlation between the changes in the eGFR and uNAG/Cre (r=-0.022, p=0.853 at 2 weeks and r=0.078, p=0.538 at 2 months). The relative change in the systolic blood pressure, hematocrit, plasma volume, and N-terminal pro-brain natriuretic peptide (NT-proBNP) were correlated with the relative change in the eGFR. In a multiple linear regression analysis, the relative change in the eGFR at 2 weeks was significantly associated with NT-proBNP, and the relative change in the uNAG/Cre was significantly associated with the use of loop diuretics and the relative change in urine osmolality at 2 weeks. Conclusion A transient decrease in the eGFR after the initiation of dapagliflozin in patients with HFrEF was not generally associated with renal tubular injury and might have been the result of hemodynamic alteration.

Effect of dapagliflozin on ventricular repolarization in patients with heart failure with reduced ejection fraction.

Whether sodium-glucose cotransporter-2 inhibitors (SGLT2is) reduce ventricular arrhythmias and sudden cardiac death is controversial. Ventricular repolarization heterogeneity is associated with ventricular arrhythmias; however, the effect of SGLT2is on ventricular repolarization in patients with heart failure with reduced ejection fraction (HFrEF) has not been fully investigated. We prospectively evaluated 31 HFrEF patients in sinus rhythm who were newly started on dapagliflozin 10 mg/day. Changes in QT interval, corrected QT interval (QTc), QT dispersion (QTD), corrected QTD (QTcD), T peak to T end (TpTe), TpTe/QT ratio, and TpTe/QTc ratio were evaluated at 1-year follow-up. QT interval, QTc interval, QTD, QTcD, TpTe, and TpTe/QTc ratio decreased significantly at 1-year follow-up (427.6 ± 52.6 ms vs. 415.4 ± 35.1 ms; p = 0.047, 437.1 ± 37.3 ms vs. 425.6 ± 22.7 ms; p = 0.019, 54.1 ± 11.8 ms vs. 47.6 ± 14.7 ms; p = 0.003, 56.0 ± 11.2 ms vs. 49.4 ± 12.3 ms; p = 0.004, 98.0 ± 15.6 ms vs. 85.5 ± 20.9 ms; p = 0.018, and 0.225 ± 0.035 vs. 0.202 ± 0.051; p = 0.044, respectively). TpTe/QT ratio did not change significantly (0.231 ± 0.040 vs. 0.208 ± 0.054; p = 0.052). QT interval, QTD, and TpTe were significantly reduced 1 year after dapagliflozin treatment in patients with HFrEF. The beneficial effect of dapagliflozin on the heterogeneity of ventricular repolarization may contribute to the suppression of ventricular arrhythmias.Registry information https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000049428 . Registry number: UMIN000044902.

Activation recovery interval as an electrocardiographic repolarization index to detect doxorubicin-induced cardiotoxicity.

BACKGROUND: It has been reported that early detection and treatment of cancer therapy- related cardiac dysfunction (CTRCD) improves its prognosis. The detailed relationships between electrocardiographic repolarization indices and decreased left ventricular function in CTRCD have not been elucidated. We closely assessed such relationships in patients with doxorubicin (DOX)-induced CTRCD. METHODS: This retrospective, single-center, cohort study included 471 consecutive patients with malignant lymphoma who received chemotherapy including DOX. Of them, 17 patients with CTRCD and 68 patients without CTRCD who underwent 12­lead electrocardiogram and an echocardiogram before and after chemotherapy were eventually analyzed. The fluctuations of the following electrocardiographic repolarization indices were evaluated in lead V5: QT, JT, T peak to T end interval (Tp-e), and activation recovery interval (ARI). These indices were corrected by heart rate with the Fridericia formula. RESULTS: The median period from the end of chemotherapy to the diagnosis of the CTRCD group was 346 days (IQR 170-1283 days). After chemotherapy, the QT interval was significantly prolonged in both with and without CTRCD groups compared with that before chemotherapy (pre QTc vs. post QTc in CTRCD group, 386 ±â€¯27 ms vs. 411 ±â€¯37 ms, p = 0.03, pre QTc vs. post QTc in non-CTRCD group, 388 ±â€¯24 ms vs. 395 ±â€¯25 ms, p = 0.04, respectively). ARIc after chemotherapy was characteristically observed only in the CTRCD group (pre ARIc vs. post ARIc in CTRCD group, 258 ±â€¯53 ms vs. 211 ±â€¯28 ms, p = 0.03, pre ARIc vs. post ARIc in non-CTRCD group, 221 ±â€¯19 ms vs. 225 ±â€¯23 ms, NS, respectively) and had negative correlations with left ventricular ejection fraction (r = -0.56, p < 0.001). Using the receiver-operating characteristic curve, the relationship between ARIc and CTRCD morbidity was examined. The optimal cut-off point of ARIc prolongation between before and after chemotherapy was 18 ms (sensitivity 75 %, specificity 79 %, area under the curve 0.76). CONCLUSIONS: ARIc prolongation may be useful in the early detection of developing late-onset chronic DOX-induced CTRCD and lead to early treatment for cardiac protection.

Delayed rupture of the iliac artery after endovascular therapy.

Iliac artery rupture during endovascular therapy (EVT) is a life-threatening complication requiring prompt diagnosis and treatment. However, delayed rupture of the iliac artery after EVT is rare, and its predictive value remains unknown. Herein, we present the case of a 75-year-old woman who developed delayed iliac artery rupture 12 h after balloon angioplasty and placement of a self-expandable stent in the left iliac artery. Hemostasis was achieved with a covered stent graft. However, the patient died of hemorrhagic shock. From the review of previous case reports and the pathological findings of the current case, increased radial force due to overlapping stent and kinking of the iliac artery may be associated with delayed iliac artery rupture. Learning objective: Delayed iliac artery rupture after endovascular therapy is rare but with a poor prognosis. Hemostasis can be achieved using a covered stent; however, the outcome could be fatal. Based on pathological findings and previous case reports, increased radial force at the stent site and kinking of the iliac artery may be associated with delayed iliac artery rupture. Self-expandable stent probably should not be overlapped at the site where kinking is likely to occur, even if long stenting is needed.

Prevalence, characteristics and cardiovascular and non-cardiovascular outcomes in patients with heart failure with supra-normal ejection fraction: Insight from the JROADHF study.

AIMS: We aimed to investigate the characteristics and prognosis of patients with heart failure (HF) with supra-normal ejection fraction (HFsnEF) compared to HF with normal ejection fraction (HFnEF). METHODS AND RESULTS: Among 11 573 patients enrolled in the nationwide registry of hospitalized patients with HF in Japan, 1943 patients (16.8%) were classified as HFsnEF (left ventricular ejection fraction [LVEF] >65%), 3277 (28.3%) as HFnEF (50% ≤ LVEF ≤65%), 2024 (17.5%) as HF with mildly reduced ejection fraction (40% ≤ LVEF <50%) and 4329 (37.4%) as HF with reduced ejection fraction (LVEF <40%). Patients with HFsnEF were older, more likely to be women, had lower natriuretic peptide values, and had smaller left ventricles than those with HFnEF. The primary endpoint, the composite of cardiovascular death or HF readmission, did not differ between HFsnEF (802/1943, 41.3%) and HFnEF (1413/3277, 43.1%) during a median follow-up period of 870 days (hazard ratio [HR] 0.96, 95% confidence interval 0.88-1.05, p = 0.346). The incidence of secondary outcomes, including all-cause, cardiovascular, and non-cardiovascular deaths and HF readmission, did not differ between HFsnEF and HFnEF. In the multivariable Cox regression analysis, HFsnEF compared to HFnEF was associated with a lower adjusted HR for HF readmission but not with the primary and other secondary endpoints. HFsnEF was associated with a higher HR for the composite endpoint and all-cause death in women, and a higher HR for all-cause death in patients with renal dysfunction. CONCLUSIONS: Heart failure with supra-normal ejection fraction is a common and distinctive phenotype, and has different characteristics and prognoses from HFnEF.

Diuretic and renal effects of angiotensin receptor-neprilysin inhibitor in patients hospitalized for acute heart failure.

In patients hospitalized for acute decompensation of heart failure (HF), the impact of angiotensin receptor-neprilysin inhibitor (ARNI) on diuresis and renal function has not been fully investigated. Patients with HF and reduced ejection fraction who were hospitalized for acute decompensation and newly initiated ARNI after hemodynamic stabilization were enrolled. Changes in urine volume (UV), body weight, estimated glomerular filtration rate (eGFR), and urine N-acetyl-beta-d-glucosaminidase (uNAG) levels before and after ARNI initiation were investigated. Changes in the diuretic response [DR, calculated as urine volume/(intravenous furosemide volume/40 mg)], N-terminal pro-brain natriuretic peptide (NT-proBNP), hematocrit, and plasma volume (PV) were also evaluated. A total of 60 patients were enrolled. ARNI was initiated at a median of 6 [5, 7] days after hospitalization. After initiation of ARNI, body weight, NT-proBNP, and PV decreased. UV and DR increased only on the day of ARNI initiation (delta UV 400 ± 957 ml and delta DR 1100 ± 3107 ml/40 mg furosemide) and then decreased to baseline levels. In the multivariable linear regression analysis, younger age, higher BMI, and higher NT-proBNP levels were significantly associated with greater UV after ARNI initiation. eGFR and uNAG did not significantly change after the initiation of ARNI [delta eGFR -1.7 ± 12.0 mL/min/1.73 m2 and delta uNAG 2.0 (-5.6, 6.9) IU/L]. In patients hospitalized for HF, the initiation of ARNI was associated with a small and transient increase in UV and DR, and was not associated with worsening of renal function or tubular injury.

Anticoagulant management during percutaneous coronary intervention for a patient with antithrombin deficiency.

Previous reports on cardiac intervention in cases with antithrombin deficiency are extremely limited. We report a case of acute coronary syndrome with antithrombin deficiency in a 62-year-old man with multiple histories of thrombosis. He had worsening chest pain, and laboratory data showed an elevated level of troponin T, suggesting acute myocardial infarction. Currently, there is no fixed anticoagulation strategy for coronary intervention in patients with antithrombin deficiency. In this case, we performed coronary intervention with heparin in addition to antithrombin concentrate. The intervention was successfully performed without thrombosis or bleeding complications. Learning objective: Antithrombin deficiency is a rare disorder and data about coronary intervention for cases with antithrombin deficiency are limited. We successfully performed intervention with our anticoagulant management and it would be beneficial for future reference.

Significance of mitral L-waves in predicting late recurrences of atrial fibrillation after radiofrequency catheter ablation.

BACKGROUND: The mitral L-wave, a prominent mid-diastolic filling wave in echocardiographic examinations, is associated with severe left ventricular diastolic dysfunction. The relationship between the mitral L-wave and outcome of catheter ablation (CA) in patients with atrial fibrillation (AF) has not been established. This study aimed to evaluate the predictive value of mitral L-waves on AF recurrence after CA. METHODS: This was a retrospective and observational study in a single center. One hundred forty-six patients (mean age; 63.9 [56.0-72.0] years, 71.9% male) including 66 non-paroxysmal AF patients (45.2%) who received a first CA were enrolled. The mitral L-waves were defined as a distinct mid-diastolic flow velocity with a peak velocity ≥20 cm/s following the E wave in the echocardiographic examinations before CA. The patients enrolled were divided into groups with (n = 31, 21.2%) and without (n = 115, 78.8%) mitral L-waves. Univariate and multivariate analyses were carried out to determine the predictive factors of late recurrences of AF (LRAFs), which meant AF recurrence later than 3 months after the CA. RESULTS: During a follow-up of 28.8 (15.0-35.8) months, the ratio of LRAFs in patients with mitral L-waves was significantly higher than that in those without mitral L-waves (15 [46.9%] vs. 16 [14.0%], p < .001). A multivariate analysis using a Cox proportional hazard model revealed that the mitral L-waves were a significant predictive factor of LRAFs (hazard ratio: 3.09, 95% confidence interval: 1.53-6.24, p = .002). CONCLUSION: The appearance of mitral L-waves could predict LRAFs after CA.

Malnutrition, hemodynamics and inflammation in heart failure with reduced, mildly reduced and preserved ejection fraction.

In patients with heart failure (HF) with reduced ejection fraction (HFrEF), malnutrition can be associated with intestinal congestion and systemic inflammation. These relationships have not been fully investigated in HF with mildly reduced EF (HFmrEF) and with preserved EF (HFpEF). We analyzed 420 patients with HF who underwent right heart catheterization. The relationships between hemodynamic parameters, C-reactive protein, and the controlling nutritional (CONUT) score were investigated in HFrEF, HFmrEF and HFpEF. The CONUT score of all patients was 2 [1, 4] (median [interquartile range]), and was not significantly different between the left ventricular EF (LVEF) categories (2 [1, 3] for HFrEF, 2 [1, 3] for HFmrEF, and 3 [1, 4] for HFpEF, p = 0.279). In multivariate linear regression analyses, there was a significant association between CRP and the CONUT score in HFmrEF and HFpEF, while brain natriuretic peptide and right atrial pressure were significantly associated with the CONUT score in HFrEF. Higher CONUT scores predicted a higher incidence of the composite endpoint of death or HF hospitalization within 12 months without an interaction with LVEF (p = 0.980). The CONUT score was an independent predictor of the composite endpoint, death, and HF hospitalization after adjustment for confounders in the multivariate analysis. In conclusion, inflammation was associated with malnutrition in HFmrEF and HFpEF, while congestion was an independent predictor of malnutrition in HFrEF. Malnutrition predicted worse outcomes regardless of LVEF.

Acute Myocarditis in a Patient Following mRNA-1273 SARS-CoV-2 Vaccination.

We herein report a case of acute myocarditis possibly related to the second dose of an mRNA-coronavirus disease 2019 vaccine in a 45-year-old woman with no remarkable medical history. She had a fever for one week following the second dose of the mRNA-1273 severe acute respiratory syndrome coronavirus 2 vaccine. One week later, she presented with chest pain and electrocardiogram changes. Her serum troponin levels were elevated upon admission. Echocardiography showed segmental wall motion abnormalities of the apex, apical portion of the anterior and inferior walls. The findings of cardiac magnetic resonance imaging were consistent with acute myocarditis.

The inducibility and focus of atrial fibrillation after ablation in patients with tachycardia-induced heart failure.

BACKGROUND: The inducibility of atrial fibrillation (AF) and incidence of nonpulmonary vein (nonPV) triggers in patients with heart failure (HF) have not been elucidated. Furthermore, the relationship between AF triggers and the change in the left ventricular (LV) function after catheter ablation (CA) remains unclear. METHODS: A total of 101 consecutive patients with a history of HF due to tachycardia who underwent CA of AF were prospectively enrolled (64.8 ± 10.7 years, male 72.3%, and paroxysmal AF 15.8%). According to the AF inducibility by isoproterenol (ISP), the patients were divided into two groups: inducible AF (66.3%) and noninducible AF (33.7%). Furthermore, inducible AF was categorized into a PV type (61.2%) and nonPV type (38.8%). This study investigated the AF recurrence and change in the LV ejection fraction (LVEF) after CA. RESULTS: AF recurred in 35 patients (34.7%) during the follow-up period (41.6 ± 26.8 months). Kaplan-Meier curves showed that patients with noninducible AF had just as bad an AF recurrence rate as those with the nonPV type. Cox proportional hazards models also revealed that noninducible AF (Hazard-ratio, 5.74; 95% CI, 1.81-18.13) was associated with a higher risk of recurrence. The LVEF significantly improved after the CA (from 49.1 ± 16.3% to 67.0 ± 7.9%). However, the nonPV type was associated with a lower improvement in the LVEF (Odds-ratio, 0.18; 95% CI, 0.05-0.70). CONCLUSION: The AF inducibility was associated with AF recurrence. Furthermore, the nonPV triggers were associated with a lesser improvement in the LVEF. Confirming the AF inducibility and triggers was important to predict the outcome after CA.

Autopsy findings of left atrial appendage closure device.

We report an autopsy case of an 80-year-old woman who underwent left atrial appendage closure with a WATCHMAN (Boston Scientific, St. Paul, MN, USA) device. This is the first report of histologic assessment following left atrial appendage closure with a WATCHMAN device at 3 months. Gross and histopathological examinations revealed neoendocardial coverage of the WATCHMAN device. Partial endothelialization was verified by CD34 staining; however, it remains unclear when complete endothelialization is likely to occur.

The role of the renal resistance index in patients with heart failure with reduced or preserved ejection fraction.

BACKGROUND: Renal impairment is a common phenomenon that portends a poor prognosis of heart failure (HF). The renal arterial resistance index (RRI) can be useful for defining renal function and predicting outcomes in patients with HF. This study aimed to investigate the determining factors of the RRI in HF patients with preserved ejection fraction (HFpEF) and with reduced EF (HFrEF). METHODS: This retrospective study included 330 patients with HF. We investigated the determining factors for the RRI and the association between the RRI and 1-year composite outcome, comprising all-cause mortality and re-hospitalization for HF. RESULTS: The independent predictors of the RRI were tricuspid regurgitation peak gradient and estimated glomerular filtration rate in HFpEF, and pulse pressure and blood urea nitrogen in HFrEF. During the follow-up, 30 (9.1%) patients presented the composite outcome. Cox proportional hazard analysis revealed the association of the RRI with the composite outcome in both HFrEF (HR 1.08; 95% CI 1.03-1.14) and HFpEF (HR 1.07; 95% CI 1.03-1.12) without an interaction (p for interaction = 0.770). CONCLUSIONS: The RRI was a consistent prognosticator in patients with HFpEF and those with HFrEF, while factors defining RRI were different between these groups.

Possible Neoangiogenesis in Achilles Tendon Xanthoma with Familial Hypercholesterolemia: A Novel Approach to Achilles Tendon Xanthoma.

Achilles tendon xanthoma (ATX) is one of the typical features of familial hypercholesterolemia (FH). The morphological evaluation of ATX by X-ray radiography is widely recognized; however, the utility of other imaging modalities remains unclear. We herein report two cases of FH in which Doppler ultrasound imaging demonstrated a microvascular flow in ATX that only rarely could be observed in normal Achilles tendons. Neoangiogenesis accompanies chronic inflammation and it may play an important role in the deposition of cholesterol crystals leading to ATX. In addition to the morphological evaluation of ATX, the assessment of neoangiogenesis may therefore be essential for the evaluation of ATX.

Relationship between the degree of renal dysfunction and the safety and efficacy outcomes in patients with atrial fibrillation receiving direct oral anticoagulants.

BACKGROUND: The clinical evaluation of a direct oral anticoagulant (DOAC) treatment for atrial fibrillation (AF) patients with renal dysfunction has not been sufficiently studied. This study aimed to evaluate the safety and efficacy of DOACs for patients with a severely impaired renal function. METHODS: This was a retrospective and observational study in a single center. We enrolled 894 consecutive AF patients who were prescribed DOACs, and divided them into three groups based on their creatinine clearance (CrCl) value: CrCl ≥ 50 mL/min group (n = 634), CrCl 30-49 mL/min group (n = 207), and CrCl 15-29 mL/min group (n = 53). We evaluated the occurrence of major bleeding (MB) as the safety outcome and thromboembolic events (TEs) as the efficacy outcome during the follow-up. RESULTS: The incidence of MB in the CrCl 15-29 mL/min group was significantly higher than in the other groups (CrCl ≥ 50 mL/min group, 0.8/100 person-years; CrCl 30-49 mL/min group, 1.2/100 person-years; CrCl 15-29 mL/min group, 9.0/100 person-years, log rank test, P < .001). On the other hand, there was no significant difference in the incidence of TEs among the three groups. A multivariate analysis using a Cox proportional hazard model adjusted for the age revealed that the CrCl 15-29 mL/min group was significantly associated with increased MB compared to the CrCl ≥ 50 mL/min group (hazard ratio: 9.76, 95% confidence interval: 2.69-35.5, P < .001). Similar results were observed when adjusting for other multiple clinical factors. CONCLUSION: This study demonstrated that the degree of renal dysfunction was a significant prognostic factor for MB in AF patients receiving DOACs.