Prognostic impact of a reduction in the fibrosis-4 index among patients hospitalized with acute heart failure.

Although the fibrosis-4 index (FIB-4) is associated with right atrial pressure or prognosis in acute heart failure (AHF), the prognostic impact of its reduction during hospitalization remains uncertain. We included 877 patients (age, 74.9 ± 12.0 years; 58% male) hospitalized with AHF. The reduction in FIB-4 was defined as: (FIB-4 on admission-FIB-4 at discharge)/FIB-4 on admission × 100. Patients were divided into low (< 1.0%, n = 293), middle (1.0-27.4%, n = 292), and high (> 27.4%, n = 292) FIB-4 reduction groups. The primary outcome was a composite of all-cause death or heart failure rehospitalization within 180 days. The median FIB-4 reduction was 14.7% (interquartile range - 7.8-34.9%). The primary outcome was observed in 79 (27.0%), 63 (21.6%), and 41 (14.0%) patients in the low, middle, and high FIB-4 reduction groups, respectively (P = 0.001). Adjusted Cox proportional-hazards analysis revealed that the middle and low FIB-4 reduction groups were associated with the primary outcome, independent of the pre-existing risk model including baseline FIB-4 ([high vs. middle] hazard ratio [HR]: 1.70, 95% confidence interval [CI]: 1.10-2,63, P = 0.017; [high vs. low] HR: 2.16, 95% CI 1.41-3.32, P < 0.001). FIB-4 reduction provided additional prognostic value to the baseline model, including well-known prognostic factors ([continuous net reclassification improvement] 0.304; 95% CI 0.139-0.464; P < 0.001; [integrated discrimination improvement] 0.011; 95% CI 0.004-0.017; P = 0.001). Additionally, the combination of the reduction in FIB-4 and brain natriuretic peptide was useful for risk stratification. In conclusion, among patients hospitalized with AHF, a greater FIB-4 reduction during hospitalization was associated with better prognoses.

Prognostic Impact of Multiple Drug Use at Discharge in Patients Hospitalized with Heart Failure.

The association between polypharmacy/multiple drug use (MDU) and prognosis in patients hospitalized with heart failure (HF) is unclear. It is also unknown whether the prognostic values of MDU vary depending on the presence/absence of a previous history of HF and preserved/reduced left ventricular ejection fraction (LVEF). We analyzed consecutive 1,034 patients hospitalized with HF (age, 74.9 ± 11.5 years; 58.7% male). MDU was defined as ≥5 drugs at discharge. The primary endpoint was a composite of all-cause death and HF readmission. MDU was observed in 695 patients (67.2%). Patients with MDU use had higher prevalences of a previous history of HF, reduced LVEF, and comorbidities than those without MDU. Cox proportional hazard analysis showed that MDU was significantly associated with the primary endpoint after adjustment for possible confounders (hazard ratio [HR], 1.36; 95% confidence interval [CI], 1.03-1.79; P = 0.030). There was significant interaction between the presence/absence of a history of HF and the prognostic impact of MDU (HF history [-]: HR, 0.86; 95% CI, 0.54-1.40; P = 0.553; HF history [+]: HR, 1.72; 95% CI, 1.16-2.55; P = 0.007; P for interaction = 0.005). However, there was no significant interaction between preserved/reduced LVEF and the prognostic impact of MDU (P for interaction = 0.274). In conclusion, MDU at discharge is an independent risk factor for the composite of death or HF readmission in patients hospitalized with HF. We observed a significant interaction between the presence of de novo versus recurrent HF and the prognostic value of MDU.

Prognostic Value of the FAN Score, a Combination of the Fibrosis-4 Index, Albumin-Bilirubin Score and Neutrophil-Lymphocyte Ratio, in Patients Hospitalized with Heart Failure.

The fibrosis-4 index, albumin-bilirubin score and neutrophil-lymphocyte ratio are all prognostic markers in patients with heart failure. Recently, the FAN score, which includes all 3 of these markers, was developed as a useful risk stratification tool in patients with cancer. However, its cut-off values have not been validated for heart failure. We aimed to investigate the optimal cut-off and prognostic values of the FAN score in patients with heart failure. We analyzed 669 consecutive patients hospitalized with heart failure (age, 75.8 ± 11.3 years). Their median values of the fibrosis-4 index, albumin-bilirubin score, and neutrophil-lymphocyte ratio at discharge were 2.12, -2.25, and 2.41, respectively. The FAN score for heart failure (HF-FAN score) was calculated using these median values. The primary outcome was a composite of all-cause death and heart failure rehospitalization. Patients were divided into 4 groups according to HF-FAN scores of 0 (n = 112), 1 (n = 231), 2 (n = 242) and 3 (n = 84). Patients with HF-FAN scores of 3 were older, had higher brain natriuretic peptide levels, and larger inferior vena cava diameters. Kaplan-Meier analysis showed a direct correlation between higher HF-FAN scores and occurrence of the primary endpoint (log-rank P < 0.001). Cox proportional hazard analysis revealed a higher HF-FAN score was significantly associated with a worse prognosis even after adjustment for possible prognostic factors. Changing from the FAN score to HF-FAN score provided significant continuous net reclassification improvement. In conclusion, the HF-FAN score at discharge was useful for risk stratification in patients hospitalized with heart failure. The HF-FAN score might be more suitable for patients with heart failure than the FAN score.

Splenic Volume Index Determined Using Computed Tomography upon Admission Is Associated with Readmission for Heart Failure Among Patients with Acute Decompensated Heart Failure.

The spleen is associated with inflammation, and the size of the spleen is affected by hemodynamic congestion and sympathetic stimulation. However, the association between splenic size and prognosis in patients with heart failure remains unknown. Between January 2015 and March 2017, we analyzed 125 patients with acute decompensated heart failure who were assessed by computed tomography (CT) on the day of admission. The spleen was measured by 3-dimensional CT and then the patients were assigned to groups according to their median splenic volume indexes (SpVi; splenic volume/body surface area). We then compared their baseline characteristics and rates of readmission for heart failure after one year. The median SpVi was 63.7 (interquartile range: 44.7-95.3) cm3/m2. Age did not significantly differ between the groups. Patients with a high SpVi had more significantly enlarged left atria and left ventricles. Multiple regression analysis identified significant positive correlations between SpVi and posterior wall thickness as well as left ventricular mass index. Kaplan-Meier analysis revealed lower event-free rates in the patients with a high, than a low SpVi (P = 0.041, log-rank test). After adjustment for potential cofounding factors, SpVi was independently associated with readmission for heart failure (Hazard ratio, 2.25; 95% confidence interval, 1.01-5.02; P = 0.047). In conclusion, increased splenic volume is independently associated with readmission for heart failure among patients with acute decompensated heart failure.

Asymptomatic Deep Venous Thrombosis After Elective Hip Surgery Could Be Allowed to Remain in Place Without Thromboprophylaxis After a Minimum 2-Year Follow-Up.

BACKGROUND: It is not clear how to treat asymptomatic deep venous thromboses (DVTs) following elective hip arthroplasty because the natural course of DVTs is unclear. It is therefore valuable to understand the natural course of DVTs and their relation to thromboprophylactic methods. METHODS: We followed 742 consecutive patients who underwent elective hip arthroplasty followed by mechanical or chemical prophylaxis of a DVT. All patients underwent preoperative and postoperative duplex ultrasonography of both limbs. Patients who developed postoperative DVT in the popliteal or calf vein were followed without thromboprophylaxis. DVT-positive patients were prospectively followed up with duplex ultrasonography at 3, 6, 12, and 24 months postoperatively. RESULTS: Incidences of preoperative and postoperative DVTs were 3.9% and 33.0%, respectively. Nonfatal pulmonary embolism (PE) occurred in 1 patient after negative echography. All DVTs that developed in the calf vein postoperatively and without anticoagulation remained benign, and 93% of the DVTs ultimately disappeared. CONCLUSION: These results confirmed that the natural course of asymptomatic distal DVTs is benign, with no risk of leading to PE. Thus, distal DVTs could be allowed to remain untreated without chemical prophylaxis to prevent PE in Asian populations.

Thrombophylaxis with low-dose, short-term fondaparinux after elective hip surgery.

Some studies have cautioned about the possibility of bleeding complications with routine use of anticoagulants like fondaparinux (FPX) for thrombophylaxis after elective hip surgery. Overdosing or prolonged periods of anticoagulant use should be avoided. We trialed a new regimen using FPX and tranexamic acid (TA) to reduce the risk of bleeding complications while maintaining efficacy in preventing deep vein thrombosis (DVT). The present study evaluated the effectiveness and safety of this regimen in 391 consecutive patients. Each patient was assigned either the FPX group, administered a once-daily subcutaneous injection of 1.5 mg of FPX on postoperative days 2, 3, and 4; or the intermittent pneumatic compression (IPC) group, which used an IPC device continuously for 1-2 days with no administration of any anticoagulant drugs. Ultrasonography was performed to diagnose DVT in all patients. No cases of fatal or symptomatic pulmonary embolism were encountered in either group, but six patients (3.1 %) in the FPX group and nine patients (6.0 %) in the IPC group showed asymptomatic distal DVT. The incidence of DVT tended to be lower (p = 0.19), volumes of intraoperative (p < 0.01) and postoperative (p < 0.01) blood loss were significantly smaller, and hemoglobin level was significantly higher in the FPX group than in the IPC group (p < 0.01). Our new thrombophylactic regimen using FPX and TA appears effective and safe for use after elective hip surgery.

A forty millimetre head significantly improves range of motion compared with a twenty eight millimetre head in total hip arthroplasty using a computed tomography-based navigation system.

PURPOSE: Larger-diameter (≥40 mm) femoral heads decrease the incidence of post-operative dislocation in total hip arthroplasty (THA). This study was conducted to discover whether larger-diameter femoral heads result in greater range of motion of the hip with the use of a computed tomography (CT)-based navigation system. METHODS: Thirty-nine primary THAs were performed via a posterolateral approach using a CT-based navigation system. The stem was inserted in the femur in line with the original femoral neck anteversion. Considering the range of motion during various daily activities which could occur without impingement, the cup anteversion was decided at 10 ° increments according to the stem anteversion. While the cup inclination was set at 40 ° in order to avoid a high inclination angle to prevent the edge roading between the HXLPE liner and ceramic head. After implantation, trial liners and femoral heads were used with either 28 or 40 mm diameter. Maximal hip flexion, extension, abduction, external rotation in extension at 0° and internal rotation angles in flexion at 90 ° were measured. The differences between the ranges of motion with the 40-mm and 28-mm heads were tested. The results were assessed with paired Student t-tests. RESULTS: The ranges of motion in flexion, extension, abduction and internal rotation angles improved significantly with the 40-mm heads compared with the 28-mm heads. The ranges of motion of cases where maximal flexion angle was 90° or less were excluded, improved significantly with the 40 mm heads. CONCLUSIONS: We concluded that the larger-diameter 40-mm femoral prosthetic heads result in greater ranges of motion in flexion, extension, abduction and internal rotation.

Fibrosis-4 index identifies worsening renal function associated with adverse outcomes in acute heart failure.

AIMS: Worsening renal function (WRF) often develops during heart failure (HF) treatment. However, prognostic implications of WRF in acute HF remain controversial, and risk stratification of WRF is challenging. Although the fibrosis-4 index (FIB-4) was initially established as a liver fibrosis marker, recent studies show that high FIB-4 is associated with venous congestion and poor prognosis in acute HF. This study aimed to evaluate whether FIB-4 could identify prognostically relevant and non-relevant WRF in patients with acute HF. METHODS AND RESULTS: We retrospectively analysed data from a single-centre registry on acute HF at our university hospital between January 2015 and June 2021. This study included patients with acute HF aged ≥20 years who were immediately hospitalized and had brain natriuretic peptide levels ≥100 pg/mL at admission. WRF was defined as increases of ≥0.3 mg/dL and >25% in serum creatinine level from admission to discharge. FIB-4 scores were calculated before discharge. The primary endpoint was all-cause mortality within 1 year of discharge. Based on the presence of WRF and whether FIB-4 scores were above the median, patients were stratified into four groups: no WRF and lower FIB-4 scores, no WRF and higher FIB-4 scores, WRF and lower FIB-4 scores, and WRF and higher FIB-4 scores. The patients were followed up via clinical visits or telephone interviews. Clinical outcomes were collected from the electronic medical records. RESULTS: Of the 969 patients hospitalized for acute HF (76 ± 11 years, 59% men), 118 patients (12%) had WRF at discharge. The median (interquartile range) FIB-4 score at discharge was 2.36 (1.55-3.25). The primary endpoint occurred in 136 patients (14.0%). The 1 year mortality rates were 10.5% in the no WRF and lower FIB-4 scores (≤2.36) group (n = 428), 16.1% in the no WRF and higher FIB-4 scores (>2.36) group (n = 423), 12.5% in the WRF and lower FIB-4 scores group (n = 56), and 25.8% in the WRF and higher FIB-4 scores group (n = 62) (P = 0.005). Kaplan-Meier analysis demonstrated higher all-cause mortality in the WRF and higher FIB-4 group (log-rank P = 0.003). In the Cox regression analysis, only the WRF and higher FIB-4 scores group was associated with an increased risk of mortality compared with the no WRF and lower FIB-4 scores group (hazard ratio = 2.11, 95% confidence interval: 1.07-4.18, P = 0.032), despite adjusting for other confounding factors. CONCLUSIONS: FIB-4 is a valuable risk stratification marker for WRF in patients with acute HF. The underlying mechanism and potential clinical importance of these observations require further investigation.

Left Atrial Remodeling Related to Disproportionately Low B-Type Natriuretic Peptide in Acute Heart Failure Patients with Atrial Fibrillation.

The diagnostic performance of B-type natriuretic peptide (BNP) for acute heart failure (HF) is impaired in patients with atrial fibrillation (AF). Increased AF burden in HF is associated with left atrial (LA) remodeling. Recent studies have revealed that LA remodeling may affect LV filling. We hypothesized that LA remodeling affects BNP secretion in acute HF conditions. The study investigated the clinical impact of LA remodeling on admission BNP levels in acute HF patients with and without AF. Consecutive acute HF hospitalized patients (n = 899) were divided into groups with (n = 382) or without AF (n = 507) and subdivided into disproportionately low BNP (LB) (≤200 pg/ml), medium BNP (200 to 600 pg/ml) and high BNP (≥600 pg/ml) subgroups. The AF group had a higher proportion of patients with LB than the non-AF group (23.6% vs 16.6%, p = 0.009). BNP levels in both groups were positively correlated with LV end-diastolic volume and negatively correlated with LV ejection fraction in both groups. In contrast, BNP was positively correlated with LA volume index in the non-AF group, but negatively correlated in the AF group. The survival rates were significantly higher in the LB group than in the other groups in non-AF. Conversely, there were no significant differences across all groups in AF patients. In conclusion, in patients with acute HF and AF, disproportionately low BNP levels are associated with LA structural remodeling and poor prognosis.

Dynamic measurements of hip movement in deep bending activities after total hip arthroplasty using a 4-dimensional motion analysis system.

Although deep hip bending activities are often required in Asian populations because of traditional lifestyles and religious practices, few have examined the required hip range of motion (ROM) in these activities after total hip arthroplasty (THA). We performed postoperative motion analysis to evaluate the differences in required ROMs between Japanese-style and Western-style deep hip bending activities, to investigate whether prosthetic impingement would occur during these activities and to clarify the necessity for precautions in these activities after THA. Japanese-style activities did not require larger hip ROMs than Western-style ones, and all required hip flexion angles were less than 120°. Prosthetic impingement was not observed, with a safety margin 10° or higher until impingement in any directions of flexion, adduction, or internal rotation for any activities. Thus, particular postoperative precautions for Japanese-style activities are not required.

Prognostic value of the liver fibrosis marker fibrosis-5 index in patients with acute heart failure.

AIMS: Recently, liver fibrosis markers, such as the fibrosis-4 index (FIB-4), have been shown to be associated with prognosis in patients with heart failure. The fibrosis-5 (FIB-5) index, which assesses albumin, alkaline phosphatase, aspartate transaminase, alanine aminotransferase and platelet count, is a simple liver fibrosis marker that was reported to be superior to FIB-4 for differentiation of liver fibrosis. This study aimed to compare the prognostic value of FIB-4 and FIB-5 in patients with heart failure. METHODS AND RESULTS: The FIB-4 and FIB-5 scores were calculated at discharge in 906 patients hospitalized with heart failure. The patients were stratified into three groups based on their FIB-5 scores: low (n = 303), middle (n = 301), and high (n = 302) FIB-5 groups. The primary endpoint was a composite of cardiac death or rehospitalization for heart failure. The low FIB-5 group was older and had larger inferior vena cava diameters and higher brain natriuretic peptide levels than the other two groups. The primary endpoint occurred in 156 (51.5%), 110 (36.5%), and 54 patients (17.9%) in the low, middle, and high FIB-5 groups, respectively (P < 0.001). On Cox proportional hazard analysis, the low FIB-5 was independently associated with the primary endpoint after adjustment for confounding factors. The association was consistent in both patients with preserved and reduced left ventricular ejection fraction (LVEF), and there was no significant interaction between LVEF phenotypes in terms of the prognostic impact of FIB-5 (P for interaction = 0.311). FIB-5 was superior to FIB-4 as a prognostic indicator of the primary endpoint (continuous net reclassification improvement, 0.530; 95% confidence interval [CI], 0.399-0.662; P < 0.001; integrated discrimination improvement, 0.072; 95% CI, 0.057-0.088; P < 0.001). CONCLUSIONS: The FIB-5 is a useful risk stratification marker with better prognostic value than FIB-4 in patients hospitalized with heart failure.

Disproportionately low BNP levels in patients of acute heart failure with preserved vs. reduced ejection fraction.

BACKGROUND: B-type natriuretic peptide (BNP) has been widely used for the diagnosis of heart failure, its severity, and prognosis. However, little is known about factors related to disproportionately low BNP levels even during acute heart failure conditions. METHODS AND RESULTS: Among 424 patients hospitalized for acute heart failure, we categorized the patients into the HFpEF (LVEF > 50%) or HFrEF (LVEF ≤ 50%) group and subdivided them into disproportionately low BNP (LB) group and high BNP (HB) group using a cut-off BNP level of 200 pg/mL at admission. The proportion of patients with LB was higher in the HFpEF group (22.2%) than in the HFrEF group (10.9%, p = 0.002). Patients with LB had a high BMI, lower blood pressure, and history of previous cardiovascular surgery in the HFpEF group, while patients in the HFrEF group had a high BMI and smaller left ventricular end-diastolic volume index. Furthermore, presence of LB in the HFrEF group was related to good prognosis, but LB in the HFpEF group was an indicator of poor prognosis as HB group. CONCLUSIONS: The factors associated with LB were different between the HFpEF and HFrEF groups. LB was related to good prognosis in HFrEF, but not in HFpEF.

Can accuracy with the iASSIST navigation be confirmed by assessment? A multi-center prospective randomized controlled trial with independent three-dimensional image assessment.

BACKGROUND: iASSIST is one of the novel accelerometer-based navigation systems for total knee arthroplasty (TKA). Although the accuracy of iASSIST compared with conventional instruments has been reported, such evaluations were performed on two-dimensional (2D) images (X-rays). This multi-center prospective randomized controlled trial aimed to assess component positioning between TKA with and without iASSIST by 3D image assessment, and to clarify whether the iASSIST provides any benefit with regard to alignment accuracy. METHODS: Eighty-three knees with primary knee osteoarthritis were enrolled in this study. iASSIST was used for distal femoral and proximal tibial resection in 42 knees (iA group) and a conventional guide was used in 41 knees (CONV group). At 6 months postoperatively, component alignment was evaluated with 3D images by the independent orthopaedic surgeons, and surgical parameters, range of motion and clinical outcomes were examined. RESULTS: The rate of knees who have the alignment within 3° of neutral compared with the iA group and CONV group were 92.9% (39/42) vs. 87.8% (36/41) for femur and 76.2% (32/42) vs. 56.1% (23/41) for tibia in the coronal plane, respectively, whereas in the sagittal plane, the rate was 85.7% (36/42) vs. 58.5% (24/41) for femur and 83.3% (35/42) vs. 78.0% (32/41) for tibia, respectively. Compared with the CONV group, the iA group had a significantly improved femoral alignment in the sagittal plane (P = 0.006). There were no clinical or patient-reported differences at 6 months postoperatively. CONCLUSIONS: The iASSIST provides technically high accuracy in femoral resection at TKA compared with a conventional procedure.

Relation of Aspartate Aminotransferase to Alanine Aminotransferase Ratio to Nutritional Status and Prognosis in Patients With Acute Heart Failure.

Elevated liver fibrosis markers are associated with worse prognosis in acute heart failure (AHF). The aspartate aminotransferase to alanine aminotransferase ratio (AAR) is one such fibrosis marker, and low ALT is a surrogate marker of malnutrition. Here, we evaluated the association between AAR and nutritional status and prognosis in patients with AHF. Consecutive 774 patients who were admitted due to AHF were divided into 3 groups according to AAR at discharge: first tertile, AAR<1.16 (n = 262); second tertile, 1.16≤AAR<1.70 (n = 257); and third tertile, AAR≥1.70 (n = 255). Nutritional indices and a composite of all-cause death or HF rehospitalization were compared in the 3 tertiles. Patients in the third AAR tertile were older and had lower body mass index than patients in other AAR tertiles. A higher AAR was associated with worse nutritional indices (i.e., controlling nutritional status score, geriatric nutritional risk index, and prognostic nutritional index). Clinical outcome rates significantly increased along AAR tertiles (first tertile, 28%; second tertile, 43%; third tertile, 58%, p < 0.001). Cox proportional hazards models including potential prognostic factors revealed high AAR was an independent prognostic factor of AHF. In conclusion, AAR at discharge may be associated with nutritional status and worse clinical outcomes in patients with AHF.

Substantially Elevated Atherosclerotic Risks in Japanese Severe Familial Hypercholesterolemia Defined by the International Atherosclerosis Society.

Background: The International Atherosclerosis Society (IAS) has proposed "severe familial hypercholesterolemia" (FH) as a phenotype with the highest cardiovascular risk. However, whether this criteria could appropriately stratify a high-risk Japanese patient with FH remains unknown. Objectives: This study sought to characterize atherosclerotic cardiovascular diseases in IAS-defined Japanese subjects with severe FH. Methods: This study analyzed 380 clinically diagnosed subjects with heterozygous FH without any history of atherosclerotic cardiovascular diseases. Severe FH was defined as untreated low-density lipoprotein cholesterol >400 mg/dL, >310 mg/dL plus 1 high-risk feature, or >190 mg/dL plus 2 high-risk features according to IAS-proposed statement. The occurrence of first and subsequent composite outcomes (cardiac [cardiac death + coronary artery disease + coronary revascularization] and noncardiac events [stroke + peripheral artery disease] was compared between subjects with severe (n = 135) and non-severe (n = 227) FH. Results: Severe FH was identified in 40.3% of study population. They had higher low-density lipoprotein cholesterol (P < 0.001) and lipoprotein(a) (P = 0.03) levels. Moreover, they more frequently received high-intensity statin (P < 0.001), PCSK9 inhibitor (P < 0.001), and lipoprotein apheresis (P = 0.01) than nonsevere FH subjects did, which resulted in a lower on-treatment low-density lipoprotein cholesterol level of subjects with severe FH (113 ± 47.2 vs 130 ± 53.9 mg/dL; P = 0.007). However, during the 7.4-year observational period, subjects with severe FH exhibited a 9.3-, 15.4-, and 5.9-fold greater risk for first composite (P < 0.001), cardiac (P < 0.001), and noncardiac outcomes (P = 0.02), respectively. Multivariate Cox proportional hazard model consistently revealed the 7.8- and 7.9-fold elevated risks of first (P < 0.001) and of subsequent (P < 0.001) composite outcomes in subjects with severe FH. Conclusions: Japanese subjects with severe FH present profound risks of both first and subsequent atherosclerotic cardiovascular diseases in the primary prevention settings. These findings support the clinical applicability of IAS-defined severe FH in Japanese patients, which identifies those who require further stringent antiatherosclerotic management.

Patients With LDLR and PCSK9 Gene Variants Experienced Higher Incidence of Cardiovascular Outcomes in Heterozygous Familial Hypercholesterolemia.

Background Patients with familial hypercholesterolemia who harbored both low-density lipoprotein receptor (LDLR) and PCSK9 (proprotein convertase subtilisin/kexin type 9) gene variants exhibit severe phenotype associated with substantially high levels of low-density lipoprotein cholesterol. In this study, we investigated the cardiovascular outcomes in patients with both LDLR and PCSK9 gene variants. Methods and Results A total of 232 unrelated patients with LDLR and/or PCSK9 gene variants were stratified as follows: patients with LDLR and PCSK9 (LDLR/PCSK9) gene variants, patients with LDLR gene variant, and patients with PCSK9 gene variant. Clinical demographics and the occurrence of primary outcome (nonfatal myocardial infarction) were compared. The observation period of primary outcome started at the time of birth and ended at the time of the first cardiac event or the last visit. Patients with LDLR/PCSK9 gene variants were identified in 6% of study patients. They had higher levels of low-density lipoprotein cholesterol (P=0.04) than those with LDLR gene variants. On multivariate Cox regression model, they experienced a higher incidence of nonfatal myocardial infarction (hazard ratio, 4.62; 95% CI, 1.66-11.0; P=0.003 versus patients with LDLR gene variant). Of note, risk for nonfatal myocardial infarction was greatest in male patients with LDLR/PCSK9 gene variants compared with those with LDLR gene variant (86% versus 24%; P<0.001). Conclusions Patients with LDLR/PCSK9 gene variants were high-risk genotype associated with atherogenic lipid profiles and worse cardiovascular outcomes. These findings underscore the importance of genetic testing to identify patients with LDLR/PCSK9 gene variants, who require more stringent antiatherosclerotic management.

Natural course of asymptomatic deep venous thrombosis in hip surgery without pharmacologic thromboprophylaxis in an Asian population.

BACKGROUND: The clinical importance of asymptomatic deep venous thrombosis in elective hip surgery is not clearly known. QUESTIONS/PURPOSES: We determined the preoperative and postoperative incidences of asymptomatic deep venous thrombosis, identified preoperative factors associated with postoperative deep venous thrombosis or pulmonary embolism, and established its natural course in patients who underwent elective hip surgery without receiving pharmacologic thromboprophylaxis. PATIENTS AND METHODS: We reviewed 184 patients who underwent consecutive elective hip surgeries with a mechanical thromboprophylaxis regimen including combined general and epidural anesthesia, intraoperative calf bandaging, early mobilization, and postoperative intermittent pneumatic compression with additional use of elastic stockings. Duplex ultrasonography was performed routinely to diagnose deep venous thrombosis in all patients before surgery and on Postoperative Days 3 and 21. All patients with postoperative deep venous thrombosis underwent additional ultrasonography at 3-month intervals, and all patients were followed postoperatively for 6 months or more. RESULTS: Preoperatively, we found asymptomatic deep venous thrombosis in two patients (1%); both thromboses had completely and spontaneously resolved by Postoperative Day 21. Postoperatively, no patients had a fatal or symptomatic pulmonary embolism or proximal deep venous thrombosis, but nine patients (5%) had asymptomatic distal deep venous thrombosis develop, with no preoperative associated factors. These nine patients were followed closely without anticoagulant drugs, and all thromboses had disappeared without pulmonary embolism or thrombophlebitis by 6 months. CONCLUSIONS: The incidence of preoperative and postoperative deep venous thrombosis was low in an Asian population having elective hip surgery and a nonpharmacologic thromboprophylaxis regimen. There were no preoperative factors associated with postoperative deep venous thrombosis, and all asymptomatic deep venous thromboses resolved spontaneously without associated pulmonary embolism or thrombophlebitis. LEVEL OF EVIDENCE: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

Diminished response to statins predicts the occurrence of heart failure after acute myocardial infarction.

BACKGROUND: Lowering low-density lipoprotein cholesterol (LDL-C) levels using a statin is a cornerstone of preventive therapeutic management following acute myocardial infarction (AMI). In addition to its anti-atherosclerotic effects, recent studies reported a lower occurrence of heart failure (HF) under statin therapy. However, there is a wide variability in statin response. The association between the response to statin and the occurrence of HF in AMI subjects remains unclear. The purpose of present study is to examine whether the variability in statin response affects HF risk after AMI. METHODS: We analyzed 505 statin-naïve AMI subjects undergoing primary percutaneous coronary intervention (PCI) who commenced atorvastatin, rosuvastatin, or pitavastatin. Statin hyporesponse was defined as a reduction in LDL-C levels <15% from baseline to 1 month after statin therapy. HF outcomes were compared between patients with and without statin hyporesponse. RESULTS: Statin hyporesponse was identified in 15.2% (77/505) of study subjects. During a median 4.4-year observational period, statin hyporesponse was associated with a greater likelihood of HF [hazard ratio (HR) =3.01, 95% confidence interval (CI): 1.27-6.79, P=0.01]. This increased HF risk in statin hyporesponders was consistently observed in a multivariate Cox proportional hazards model (HR =2.74, 95% CI: 1.01-6.75, P=0.04), a propensity score-matched cohort (HR =12.30, 95% CI: 1.50-100.3, P=0.01) and in an inverse probability of treatment weights analysis with average treatment effects (coefficient =7.02, 95% CI: 2.29-21.58, P=0.0006). CONCLUSIONS: Hyporesponse to statins increases HF risk after AMI. Our findings highlight statin hyporesponse as a high-risk feature associated with HF events.