Enhancement of bicycle exercise capacity in patients with chronotropic incompetence through closed-loop stimulation: a randomized crossover trial.

AIMS: This study aimed to investigate the effectiveness of closed-loop stimulation (CLS) pacing compared with the traditional DDD mode in patients with chronotropic incompetence (CI) using bicycle-based cardiopulmonary exercise testing (CPET). METHODS AND RESULTS: This single-centre, randomized crossover trial involved 40 patients with CI. Patients were randomized to receive either DDD-CLS or DDD mode pacing for 2 months, followed by a crossover to the alternative mode for an additional 2 months. Bicycling-based CPET was conducted at the 3- and 5-month follow-up visits to assess exercise capacity. Other cardiopulmonary exercise outcome measures and health-related quality of life (QoL) were also assessed. DDD-CLS mode pacing significantly improved exercise capacity, resulting in a peak oxygen uptake (14.8 ± 4.0 vs. 12.0 ± 3.6 mL/kg/min, P < 0.001) and oxygen uptake at the ventilatory threshold (10.0 ± 2.2 vs. 8.7 ± 1.8 mL/kg/min, P < 0.001) higher than those of the DDD mode. However, there were no significant differences in other cardiopulmonary exercise outcome measures such as ventilatory efficiency of carbon dioxide production slope, oxygen uptake efficiency slope, and end-tidal carbon dioxide between the two modes. Patients in the DDD-CLS group reported a better QoL, and 97.5% expressed a preference for the DDD-CLS mode. CONCLUSION: DDD-CLS mode pacing demonstrated improved exercise capacity and QoL in patients with CI, highlighting its potential as an effective pacing strategy for this patient population.

Diagnosis of kidney insufficiency by using the pressure waveforms of wrist-type sphygmomanometers: toward a convenient point-of-care device.

OBJECTIVES: Digital sphygmomanometers have been used for more than 40 years in Western medicine for accurately measuring systolic and diastolic blood pressures, which are vital signs observed for the diagnosis of different diseases. Similarly, traditional Chinese medicine (TCM) has been using wrist pulse diagnosis for thousands of years. Some studies have combined digital wrist pulse signals and the diagnosis method of TCM to quantify pulse waves and identify diseases. However, the effectiveness of this approach is limited because of scattered methods and complex pathological features. Moreover, the literature on TCM does not provide quantitative data or objective indicators. METHODS: In this prospective study, we developed a diagnostic system that contains a modified sphygmomanometer. In addition, we designed a procedure for analyzing pulse waves with 156 features of harmonic modes and a decision tree method for diagnosing kidney insufficiency. RESULTS: In the decision tree method, at least three features of harmonic modes can achieve an accuracy of 0.86, a specificity of 0.91, and a Cohen's kappa coefficient of 0.72. By comparison, the random forest method can achieve an accuracy of 0.99, a specificity of 0.99, and a Cohen's kappa coefficient of 0.94 within 200 trees. The results of this study indicated that even in patients with kidney insufficiency and complex etiology, common features can be distinguished by identifying changes in pulse waveforms. CONCLUSION: By using the modified sphygmomanometer to measure blood pressure, people can monitor their health status and take care of it in advance by simply measuring their blood pressure.

In Silico Evaluation of HN-N07 Small Molecule as an Inhibitor of Angiogenesis and Lymphangiogenesis Oncogenic Signatures in Non-Small Cell Lung Cancer.

Tumor angiogenesis and lymphangiogenesis pathways have been identified as important therapeutic targets in non-small cell lung cancer (NSCLC). Bevacizumab, which is a monoclonal antibody, was the initial inhibitor of angiogenesis and lymphangiogenesis that received approval for use in the treatment of advanced non-small cell lung cancer (NSCLC) in combination with chemotherapy. Despite its usage, patients may still develop resistance to the treatment, which can be attributed to various histological subtypes and the initiation of treatment at advanced stages of cancer. Due to their better specificity, selectivity, and safety compared to chemotherapy, small molecules have been approved for treating advanced NSCLC. Based on the development of multiple small-molecule antiangiogenic drugs either in house and abroad or in other laboratories to treat NSCLC, we used a quinoline-derived small molecule-HN-N07-as a potential target drug for NSCLC. Accordingly, we used computational simulation tools and evaluated the drug-likeness properties of HN-N07. Moreover, we identified target genes, resulting in the discovery of the target BIRC5/HIF1A/FLT4 pro-angiogenic genes. Furthermore, we used in silico molecular docking analysis to determine whether HN-N07 could potentially inhibit BIRC5/HIF1A/FLT4. Interestingly, the results of docking HN-N07 with the BIRC5, FLT4, and HIF1A oncogenes revealed unique binding affinities, which were significantly higher than those of standard inhibitors. In summary, these results indicate that HN-N07 shows promise as a potential inhibitor of oncogenic signaling pathways in NSCLC. Ongoing studies that involve in vitro experiments and in vivo investigations using tumor-bearing mice are in progress, aiming to evaluate the therapeutic effectiveness of the HN-N07 small molecule.

Multi-Omics Identification of Genetic Alterations in Head and Neck Squamous Cell Carcinoma and Therapeutic Efficacy of HNC018 as a Novel Multi-Target Agent for c-MET/STAT3/AKT Signaling Axis.

Amongst the most prevalent malignancies worldwide, head and neck squamous cell carcinoma (HNSCC) is characterized by high morbidity and mortality. The failure of standard treatment modalities, such as surgery, radiotherapy, and chemotherapy, demands the need for in-depth understanding of the complex signaling networks involved in the development of treatment resistance. A tumor's invasive growth and high levels of intrinsic or acquired treatment resistance are the primary causes of treatment failure. This may be a result of the presence of HNSCC's cancer stem cells, which are known to have self-renewing capabilities that result in therapeutic resistance. Using bioinformatics methods, we discovered that elevated expressions of MET, STAT3, and AKT were associated with poor overall survival in HNSCC patients. We then evaluated the therapeutic potential of our newly synthesized small molecule HNC018 towards its potential as a novel anticancer drug. Our computer-aided structure characterization and target identification study predicted that HNC018 could target these oncogenic markers implicated in HNSCC. Subsequently, the HNC018 has demonstrated its anti-proliferative and anticancer activities towards the head and neck squamous cell carcinoma cell lines, along with displaying the stronger binding affinities towards the MET, STAT3, and AKT than the standard drug cisplatin. Reduction in the clonogenic and tumor-sphere-forming ability displays HNC018's role in decreasing the tumorigenicity. Importantly, an vivo study has shown a significant delay in tumor growth in HNC018 alone or in combination with cisplatin-treated xenograft mice model. Collectively with our findings, HNC018 highlights the desirable properties of a drug-like candidate and could be considered as a novel small molecule for treating head and neck squamous cell carcinoma.

Haptoglobin-Conjugated Gold Nanoclusters as a Nanoantibiotic to Combat Bacteremia.

Gold nanoclusters have revealed great potential as nanoantibiotics due to their superior chemical and physical characteristics. In this study, a peptide with 83 amino acids derived from haptoglobin was utilized as a surface ligand to synthesize gold nanoclusters via a facile hydrothermal approach. Characterization of the structural and optical properties demonstrated the successful synthesis of derived haptoglobin-conjugated gold nanoclusters. The spherical derived haptoglobin-conjugated gold nanoclusters exhibited a (111) plane of cubic gold and an ultra-small size of 3.6 ± 0.1 nm. The optical properties such as ultraviolet-visible absorption spectra, X-ray photoelectron spectroscopy spectra, fluorescence spectra, and Fourier transform infrared spectra also validated the successful conjugation between the derived haptoglobin peptide and the gold nanoclusters surface. The antibacterial activity, reactive oxygen species production, and antibacterial mechanisms of derived haptoglobin-conjugated gold nanoclusters were confirmed by culturing the bacterium Escherichia coli with hemoglobin to simulate bacteremia. The surface ligand of the derived haptoglobin peptide of derived haptoglobin-conjugated gold nanoclusters was able to conjugate with hemoglobin to inhibit the growth of Escherichia coli. The derived haptoglobin-conjugated gold nanoclusters with an ultra-small size also induced reactive oxygen species production, which resulted in the death of Escherichia coli. The superior antibacterial activity of derived haptoglobin-conjugated gold nanoclusters can be attributed to the synergistic effect of the surface ligand of the derived haptoglobin peptide and the ultra-small size. Our work demonstrated derived haptoglobin-conjugated gold nanoclusters as a promising nanoantibiotic for combating bacteremia.

The Antihypertensive Effects and Safety of LCZ696 in Patients with Hypertension: A Systemic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: The management of hypertension remains suboptimal throughout the world. METHODS: We performed a random-effects model meta-analysis of randomized controlled trials to determine the effectiveness and safety of sacubitril/valsartan (LCZ696) for the treatment of high arterial pressure. Relevant published articles from PubMed, Cochrane base, and Medline were examined, and the last search date was December 2020. Only published randomized controlled trials and double-blind studies were selected for further analysis. The mean reductions in systolic blood pressure (msSBP) and diastolic blood pressure (msDBP) in the sitting position, as well as the mean reductions in ambulatory systolic blood pressure (maSBP) and ambulatory diastolic blood pressure (maDBP), were assumed as efficacy endpoints. Adverse events (AEs) were considered as safety outcomes. RESULTS: Ten studies with a total of 5931patients were included for analysis. Compared with placebo, LCZ696 had a significant reduction in msSBP (weight mean difference (WMD) = -6.52 mmHg, 95% confidence interval (CI): -8.57 to -4.47; p < 0.001), msDBP (WMD = -3.32 mmHg, 95% CI: -4.57 to -2.07; p < 0.001), maSBP (WMD = -7.08 mmHg, 95% CI: -10.48 to -3.68; p < 0.001), maDBP (WMD = -3.28 mmHg, 95% CI: -4.55 to -2.02, p < 0.001). In subgroup analysis, only 200 mg and 400 mg LCZ696 showed a significant BP reduction. There was no difference in the AE rate between the LCZ696 and placebo groups (WMD = 1.02, 95% CI: 0.83 to 1.27, p = 0.54). Egger's test revealed a potential publication bias for msSBP (p = 0.025), but no publication bias for other outcomes. CONCLUSION: LCZ696 may reduce blood pressure more efficaciously than traditional therapy in hypertensive patients without increasing adverse effects.

Successful bailout stenting strategy against rare spontaneous retrograde dissection of partially absorbed magnesium-based resorbable scaffold: A case report.

BACKGROUND: In the development of coronary stent technology, bioresorbable scaffolds are promising milestones in improving the clinical treatment of coronary artery disease. The "leave nothing behind" motto is the premise of the fourth revolution in percutaneous coronary intervention (PCI). Studies proving the safety and efficacy of the magnesium-based resorbable scaffolds (MgBRSs) include the BIOSOLVE-I and BIOSOLVE-II trials and the latest BIOSOLVE-IV registry. However, spontaneous retrograde dissection of a partially absorbed MgBRS may still occur, albeit rarely. CASE SUMMARY: We describe an unusual case of coronary artery disease in a patient who had undergone a successful PCI 8 mo earlier, where an MgBRS was implanted into the left anterior descending artery (LAD) and left circumflex artery with drug-coated balloons for a ramus intermedius branch stenosis to achieve the "leave nothing behind" therapeutic intention and was currently presenting with a gradual worsening of chest tightness. The distal edge vascular response, during subsequent attempts with balloon angioplasty was performed smoothly. However, spontaneous retrograde dissection of a partially absorbed MgBRS in the LAD ensued. Successful bailout stenting was performed with revascularization of the entry and exit sites created by spontaneous dissection and complete sealing of the intramural hematoma. The patient recovered well and was discharged after 2 d of intervention. When followed up in August 2020 (7 mo later), the patient showed uneventful recovery. CONCLUSION: Spontaneous retrograde dissection of a partially absorbed MgBRS was successfully treated using bailout sirolimus-eluting coronary stent strategy.

Amlodipine/valsartan fixed-dose combination treatment in the management of hypertension: A double-blind, randomized trial.

BACKGROUND: To compare the fixed-dose combination (FDC) of amlodipine/valsartan 5/80 mg with valsartan 160 mg monotherapy for efficacy and safety in hypertensive patients. METHODS: We designed this double-blind, randomized, and noninferiority trial in which patients with elevated systolic blood pressure (SBP) and/or diastolic blood pressure (DBP) were randomly assigned to receive amlodipine/valsartan 5/80 mg FDC or valsartan 160 mg monotherapy for 8 weeks. The primary endpoint was changes in office SBP and DBP from baseline to 8 weeks. Twenty-four-hour blood pressure (BP) and the incidence of adverse events were recorded. RESULTS: A total of 42 patients underwent randomization. At 8 weeks, office SBP changes were -16.5 ± 15.5 mmHg (p < 0.001) with amlodipine/valsartan 5/80 mg FDC and -6.9 ± 11.4 mmHg (p = 0.012) with valsartan 160 mg monotherapy while corresponding changes in office DBP were -9.8 ± 7.7 mmHg (p < 0.001) and -2.5 ± 6.6 mmHg (p = 0.095), respectively. The between-group differences were -9.6 mmHg (95% CI, -18.1 to -1.1; p = 0.028) for SBP and -7.3 mmHg (95% CI, -11.8 to -2.8; p = 0.002) for DBP. Furthermore, reductions in both 24-hour SBP (-9.2 mmHg; 95% CI, -16.4 to -2.1; p = 0.013) and DBP (-4.6 mmHg; 95% CI, -9.2 to -0.1; p = 0.048) were consistently greater with amlodipine/valsartan 5/80 mg FDC than with valsartan 160 mg. Overall, 27 and 23 adverse events occurred in the amlodipine/valsartan 5/80 mg FDC group and in the valsartan 160 mg monotherapy group, respectively. The majority were mild and were not related to study medications. There were no significant differences in safety between two treatments. CONCLUSION: Efficacy of amlodipine/valsartan 5/80 mg FDC was superior to that of valsartan 160 mg monotherapy while both treatments were well-tolerated.

A method to measure the extent of myocardial ischemia and steal with SPECT myocardial blood flow quantitation.

OBJECTIVE: We introduced a method to measure the extent of myocardial ischemia and steal with SPECT MBF quantitation. METHODS: Eighty-seven patients who received rest/Dipyridamole-stress 99mTc-Sestamibi (MIBI) dynamic SPECT scans and coronary angiography were included. Dynamic SPECT images were reconstructed with full physical corrections. The one-tissue kinetic model was utilized to quantify K1 and further converted to MBF with required corrections. Rest MBF, stress MBF and myocardial flow reserve (MFR) were converted to a flow status polar map by a flow diagram. Extents of 7 flow statuses were verified their cutoff points for detecting stenoses. The diagnostic performance (DP) was compared to that of MFR. RESULTS: Cutoff point of the extent to detect ≥ 50% stenosis was 3.01% for ischemia-steal status and 20.3% for the combined status of ischemia-steal and moderate. Using these criteria, sensitivity, specificity and accuracy to detect ≥ 50% stenosis were (80%, 75%, 79%) and (86%, 68%, 80%) for ≥ 70% stenosis. The DP was superior to that of MFR < 2.0 criterion (≥ 50%: 70%, 63%, 69%; ≥ 70%: 73%, 61%, 69%) (all p < 0.015). CONCLUSION: SPECT MBF quantitation integrated with the flow diagram can measure the extent of myocardial ischemia and steal which appeared more accurate to detect angiographic stenoses than the single MFR parameter.

Comparison of Arrhythmia Detection by 24-Hour Holter and 14-Day Continuous Electrocardiography Patch Monitoring.

BACKGROUND: Although 24-hour Holter monitoring is routinely used for patients with suspected paroxysmal arrhythmia, its sensitivity in detecting such arrhythmias is insufficient. METHODS: We compared a 14-day electrocardiography (ECG) monitor patch - a single-use, noninvasive, waterproof, continuous monitoring patch - with a 24-hour Holter monitor in 32 consecutive patients with suspected arrhythmia. RESULTS: The 14-day ECG patch was well tolerated, and its rates of detection of relevant arrhythmias on days 1, 3, 7, and 14 were 13%, 28%, 47%, and 66%, respectively. The detection rate of paroxysmal arrhythmias was significantly higher for the 14-day ECG patch than for the 24-hour Holter monitor (66% vs. 9%, p < 0.001). Among the 32 patients, 202 atrial fibrillation or atrial flutter episodes were detected in 6 patients (22%) with the 14-day ECG patch; however, only 1 atrial fibrillation episode was detected in a patient (3%, p < 0.05) with the 24-hour Holter monitor. Other clinically relevant arrhythmias recorded on the 14-day ECG patch included 21 (65.5%) episodes of supraventricular tachycardia, 2 (6.3%) long pause, and 2 (6.3%) ventricular arrhythmias. The mean dermal response score immediately after removal of the 14-day ECG patch from the patients was 0.64, which indicated minimal erythema. CONCLUSIONS: The 14-day ECG patch was well tolerated and allowed for longer continuous monitoring than the 24-hour Holter monitor, thus resulting in improved clinical accuracy in the detection of paroxysmal arrhythmias. Future studies should examine the long-term effectiveness of 14-day ECG patches for managing selected patients.

Antithrombotic Strategies in Patients with Atrial Fibrillation Following Percutaneous Coronary Intervention: A Systemic Review and Network Meta-Analysis of Randomized Controlled Trials.

Up to 10% of patients with atrial fibrillation (AF) undergo percutaneous coronary intervention (PCI). A systematic review and network meta-analysis were conducted by searching PubMed, Embase, and the Cochrane database of systematic reviews for randomized control trials that studied the safety and efficacy of different antithrombotic strategies in these patients. Six studies, including 12,158 patients were included. Compared to that in the triple antithrombotic therapy group (vitamin K antagonist (VKA) plus P2Y12 inhibitor and aspirin), thrombolysis in myocardial infarction (TIMI) major bleeding was significantly reduced in the dual antithrombotic therapy (non-vitamin K oral anticoagulants (NOACs) plus P2Y12 inhibitor) group by 47% (Odds ratio (OR), 0.53; 95% credible interval [CrI], 0.35-0.78; I2 = 0%). Besides, NOAC plus a P2Y12 inhibitor was associated with less intracranial hemorrhage compared to VKA plus single antiplatelet therapy (OR: 0.20, 95% CrI: 0.05-0.77). There was no significant difference in the trial-defined major adverse cardiac events or the individual outcomes of all-cause mortality, cardiovascular death, myocardial infarction, stroke or stent thrombosis among all antithrombotic strategies. In conclusion, antithrombotic strategy of NOACs plus P2Y12 inhibitor is safer than, and as effective as, the strategies including aspirin when used in AF patients undergoing PCI.

Noninvasive Nuclear SPECT Myocardial Blood Flow Quantitation to Guide Management for Coronary Artery Disease.

Recently, myocardial blood flow quantitation with dynamic SPECT has been validated to enhance the detection of multivessel coronary artery disease (CAD) and conclude equivocal SPECT myocardial perfusion study. This advance opened an important clinical application to utilize the tool in guiding CAD management for area where myocardial perfusion tracers for PET are unavailable or unaffordable. We present a clinical patient with ongoing recursive angina who underwent multiple nuclear stress tests for a sequence of CAD evaluation in 26 months and demonstrated that SPECT myocardial blood flow quantitation properly guided CAD management to warrant patient outcome.

Determinants of Treatment Modification in Hypercholesterolemic Patients.

BACKGROUND: There is a lack of knowledge of those contemporary factors associated with modifying subtherapeutic treatments in hypercholesterolemic patients. The aim of this study was to assess determinants of treatment modification in patients not attaining their low-density lipoprotein cholesterol goals. METHODS: The CEntralized Pan-Asian survey on tHE Under-treatment of hypercholeSterolemia enrolled patients taking stable lipid-lowering medications. The study physicians then determined existing patient treatments, which were to be continued or modified when treatments failed. The patient questionnaire surveying patient attitudes and perceptions toward their hypercholesterolemia management was prospectively collected. The odds ratios (ORs) (95% confidence intervals) were calculated. RESULTS: Among the 420 patients included for analysis, 35.7% were designated for planned treatment modification. Those patients assigned to treatment modification were more likely to have a family history of premature coronary heart disease (40% vs. 19%), an indication for secondary prevention (76% vs. 61%), elevated triglyceride (60% vs. 48%) and fasting sugar (84% vs. 67%), and were less adherent to their medications (29% vs. 12%) than patients assigned to treatment continuation. Patient recognition of treatment failure [OR, 1.82 (1.13-2.94)], the lower frequency of cholesterol checkup [OR, 2.40 (1.41-4.08)], patient satisfaction with provided cholesterol information [OR, 2.30 (1.21-4.39)], and their feelings toward cholesterol management [OR, 0.25 (0.10-0.62) and 3.80 (2.28-6.32)] for confusion and no strong feeling, respectively were determinants of the treatment modification assignment. CONCLUSIONS: There was a large gap between evidence-based goals and modification of subtherapeutic treatments, particularly among patients with lower treatment satisfaction and better compliance. Our findings have emphasized the need to further reduce inertia in implementing hypercholesterolemia management.

SPECT myocardial blood flow quantitation toward clinical use: a comparative study with 13N-Ammonia PET myocardial blood flow quantitation.

OBJECTIVES: The aim of this study was to evaluate the accuracy of myocardial blood flow (MBF) quantitation of 99mTc-Sestamibi (MIBI) single photon emission computed tomography (SPECT) compared with 13N-Ammonia (NH3) position emission tomography (PET) on the same cohorts. BACKGROUND: Recent advances of SPECT technologies have been applied to develop MBF quantitation as a promising tool to diagnose coronary artery disease (CAD) for areas where PET MBF quantitation is not available. However, whether the SPECT approach can achieve the same level of accuracy as the PET approach for clinical use still needs further investigations. METHODS: Twelve healthy volunteers (HVT) and 16 clinical patients with CAD received both MIBI SPECT and NH3 PET flow scans. Dynamic SPECT images acquired with high temporary resolution were fully corrected for physical factors and processed to quantify K1 using the standard compartmental modeling. Human MIBI tracer extraction fraction (EF) was determined by comparing MIBI K1 and NH3 flow on the HVT group and then used to convert flow values from K1 for all subjects. MIBI and NH3 flow values were systematically compared to validate the SPECT approach. RESULTS: The human MIBI EF was determined as [1.0-0.816*exp(-0.267/MBF)]. Global and regional MBF and myocardial flow reserve (MFR) of MIBI SPECT and NH3 PET were highly correlated for all subjects (global R2: MBF = 0.92, MFR = 0.78; regional R2: MBF ≥ 0.88, MFR ≥ 0.71). No significant differences for rest flow, stress flow, and MFR between these two approaches were observed (All p ≥ 0.088). Bland-Altman plots overall revealed small bias between MIBI SPECT and NH3 PET (global: ΔMBF = -0.03Lml/min/g, ΔMFR = 0.07; regional: ΔMBF = -0.07 - 0.06 , ΔMFR = -0.02 - 0.22). CONCLUSIONS: Quantitation with SPECT technologies can be accurate to measure myocardial blood flow as PET quantitation while comprehensive imaging factors of SPECT to derive the variability between these two approaches were fully addressed and corrected.

SPECT Myocardial Blood Flow Quantitation Concludes Equivocal Myocardial Perfusion SPECT Studies to Increase Diagnostic Benefits.

Recently, myocardial blood flow quantitation with dynamic SPECT/CT has been reported to enhance the detection of coronary artery disease in human. This advance has created important clinical applications to coronary artery disease diagnosis and management for areas where myocardial perfusion PET tracers are not available. We present 2 clinical cases that undergone a combined test of 1-day rest/dipyridamole-stress dynamic SPECT and ECG-gated myocardial perfusion SPECT scans using an integrated imaging protocol and demonstrate that flow parameters are capable to conclude equivocal myocardial perfusion SPECT studies, therefore increasing diagnostic benefits to add value in making clinical decisions.

The association between low-density lipoprotein cholesterol goal attainment, physician and patient attitudes and perceptions, and healthcare policy.

AIM: Withholding effective treatment is clinically prevalent. The CEntralized Pan-Asian survey on tHE Under-treatment of hypercholeSterolemia (CEPHEUS-PA) indicated suboptimal low-density lipoprotein cholesterol (LDL-C) goal attainment in Taiwan, which may be attributable to clinical inertia. We herein analyzed the Taiwanese cohort in the CEPHEUS-PA to identify key elements regarding clinical inertia and unsatisfactory LDL-C control. METHODS: A questionnaire regarding the attitudes and perceptions for each physician and patient was included in the CEPHEUS-PA. Physicians completed the physician questionnaire before enrolling patients, who completed the patient questionnaire before the assessment. RESULTS: The National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) guideline was used by 81.8% of physicians to establish the individual therapeutic targets; 50.2% of patients failed to take medications persistently. Regarding perceptions to hypercholesterolemia management, 75.9% of physicians were confident of having a sufficient number of patients at cholesterol targets; 80.2% and 65.9% of patients felt satisfied and motivated, respectively, but 46.0% had no strong feeling. The healthcare reimbursement policy used for treatment guidance was a significant determinant for LDL-C goal attainment (OR=0.32, 95% CI: 0.15-0.69, P=0.006) in addition to patient compliance. Low patient involvement indexed by having no strong feeling was associated with poor LDL-C control (OR=0.73, 95% CI: 0.56-0.95, P=0.020). CONCLUSIONS: The referenced healthcare reimbursement policy, poor patient compliance, and low patient involvement with hypercholesterolemia management were associated with failure of LDL-C control. Our findings highlight the need to overcome those barriers to improve the under-treatment of hypercholesterolemia.

Determinants of low-density lipoprotein cholesterol goal attainment: Insights from the CEPHEUS Pan-Asian Survey.

BACKGROUND: Previous studies have reported that the attainment of goals for low-density lipoprotein cholesterol (LDL-C) are globally suboptimal, but contemporary data are scarce. The CEntralized Pan-Asian survey on tHE Under-treatment of hypercholeSterolemia (CEPHEUS-PA) is the largest evaluation of pharmacological treatment for hypercholesterolemia in Asia. The study reported here analyzed the Taiwan cohort in CEPHEUS-PA to identify the determinants of successful treatment. METHODS: The patients eligible for this study were adults (≥18 years old) with hypercholesterolemia and with at least two coronary heart disease (CHD) risk factors who had been receiving lipid-lowering drugs for at least 3 months before enrollment, without adjustment for at least 6 weeks before enrollment. Demographic and clinical information and lipid concentrations were recorded. Cardiovascular risk levels and LDL-C targets were determined using the updated Adult Treatment Panel III. RESULTS: In this group of 999 Taiwanese patients, 50%, 25%, and 24% had LDL-C goals set at <70 mg/dL, <100 mg/dL, and <130 mg/dL, respectively. The overall attainment rate was 50%, with the lowest rate in patients set at the most stringent target (22%), followed by those whose therapeutic goals were <100 mg/dL (69%) and <130 mg/dL (87%). The success of LDL-C control was lower in patients with multiple risk factors other than CHD or its equivalents than in those without these multiple risk factors (37% vs. 53%, p < 0.001), and lower in patients with metabolic syndrome than in those without (43% vs. 66%, p < 0.001). Baseline LDL-C and cardiovascular risk were inversely associated with goal attainment, whereas treatment with statins was directly associated with the achievement of LDL-C goals. Patients with diabetes (odds ratio 0.49, 95% confidence interval 0.29-0.84, p = 0.010) and with metabolic syndrome (odds ratio 0.15, 95% confidence interval 0.05-0.40, p < 0.001) were less likely to be treated with statins. CONCLUSION: This study showed that there is a discrepancy between the updated Adult Treatment Panel III recommendations for LDL-C control and the control attained by this group of Taiwanese patients. In particular, treatment with statins was largely underused in patients with diabetes and in those with metabolic syndrome. These findings highlight the need for more intensive treatment in high-risk patients and those with multiple risk factors, particularly patients with metabolic syndrome.

Gender and Age Differences in Short- and Long-Term Outcomes Following Primary Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction.

BACKGROUND: Studies have reported that women with ST elevation myocardial infarction (STEMI) have worse short- and long-term outcomes than men. It has not yet been confirmed whether these differences reflect differences in age between men and women. METHODS: We retrospectively enrolled 1035 consecutive STEMI patients treated with primary percutaneous coronary intervention (PCI). Baseline clinical characteristics, coronary anatomy, and outcome were compared between young (< 65 years old) and older patients (≥ 65 years old) of both sexes. RESULTS: Younger women presented with a lower incidence of typical angina (83% vs. 93%, p = 0.03), single-vessel disease (21% vs. 35%, p = 0.03), and total occlusion of infarct-related artery (65% vs. 83%, p = 0.001) than younger men, with no gender difference noted in the older group. Younger women in the study had a higher incidence of reinfarction, heart failure requiring admission, or mortality (23% vs. 6%, p < 0.001) during follow-up, compared with younger men, with no gender difference in the older group. Using the Kaplan-Meier analysis, younger women had lower rates of event-free survival (p < 0.001 by log-rank test) than younger men, with no gender difference in the older group. In multivariate analysis, age could predict long-term outcome in men (Hazard ratio 4.43, 95% confidence interval: 2.89-6.78, p < 0.001) but not in women. CONCLUSIONS: In STEMI patients receiving primary PCI, sex-related long-term outcome differences were age-dependent, with younger women likely to have a worse long-term outcome when compared with younger men. KEY WORDS: Coronary heart disease; Gender; Myocardial infarction.

Application of the Sequential Organ Failure Assessment score for predicting mortality in patients with acute myocardial infarction.

BACKGROUND: Thrombolysis in Myocardial Infarction (TIMI) score and Global Registry of Acute Coronary Events (GRACE) score have been validated as predictors of death in patients with acute myocardial infarction (AMI). This study was undertaken to determine whether the Sequential Organ Failure Assessment (SOFA) score had good accuracy for predicting mortality in AMI patients, and to compare the discriminatory performance of the 3 risk scores (RSs). METHODS: This was a retrospective study. We calculated the TIMI RS, GRACE RS, and SOFA score for 726 consecutive AMI patients. The study endpoint was all-cause mortality. All patients were followed up for at least 3 years or until the occurrence of death. The area under the receiver operating characteristic curve (AUC) was used to evaluate the predictive ability of each score at different time points. RESULTS: For in-hospital death, the AUC were 0.67 for TIMI RS, 0.73 for GRACE RS, and 0.79 for SOFA score (P<0.001, respectively). However, the SOFA score and GRACE RS were significantly better for predicting the 1-year (P<0.001, respectively) and 3-year (P<0.001, respectively) mortality than the TIMI RS was. Multivariate Cox regression analysis revealed that the SOFA score was an independent predictor of long-term mortality in AMI patients [hazard ratio (HR), 1.313; 95% CI, 1.191-1.447]. CONCLUSIONS: The SOFA score provides potentially valuable prognostic information on clinical outcome when applied to patients with AMI. Compared with TIMI RS, both SOFA score and GRACE RS provide better discrimination for long-term mortality in patients presenting with AMI.