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To determine if an electrocardiogram-based artificial intelligence system can identify pneumothorax prior to radiological examination.This is a single-center, retrospective, electrocardiogram-based artificial intelligence (AI) system study that included 107 ECGs from 98 pneumothorax patients. Seven patients received needle decompression due to tension pneumothorax, and the others received thoracostomy due to instability (respiratory rate ≥ 24 breaths/min; heart rate, 60 beats/min or 120 beats/min; hypotension; room air OThe areas under the receiver operating characteristic (ROC) curves (AUCs) of the DLM in the validation cohort and competition set were 0.947 and 0.957, respectively. The sensitivity and specificity of our DLM were 94.7% and 88.1% in the validation cohort, respectively, which were significantly higher than those of all physicians. Our DLM could also recognize the location of pneumothorax with 100% accuracy. Lead-specific analysis showed that lead I ECG made a major contribution, achieving an AUC of 0.930 (94.7% sensitivity, 86.0% specificity). The inclusion of the patient characteristics allowed our AI system to achieve an AUC of 0.994.The present AI system may assist the medical system in the early identification of pneumothorax through 12-lead ECG, and it performs as well with lead I ECG alone as with 12-lead ECG.

Background Chest pain is the most common symptom of aortic dissection (AD), but it is often confused with other prevalent cardiopulmonary diseases. We aimed to develop deep-learning models (DLMs) with ECG and CXR features to detect AD and evaluate their performance. Methods This study included 43,473 patients in the emergency department (ED) between July 2012 and December 2019 for retrospective DLM development. A development cohort including 49,071 ED records (120 AD-type A and 64 AD-type B) was used to train DLMs for ECG and CXR, and 9,904 independent ED records (40 AD-type A and 34 AD-type B) were used to validate DLM performance. Human–machine competitions of ECG and CXR were conducted. Patient characteristics and laboratory results were used to enhance the diagnostic accuracy. The DLM-enabled AD diagnostic process was prospectively evaluated in 25,885 ED visits. Results The AUCs of the ECG and CXR models were 0.918 and 0.857 for detecting AD in a human–machine competition, respectively, which were better than those of the participating physicians. In the validation cohort, the AUCs of the integrated model were 0.882, 0.960, and 0.813 in all AD, AD-type A, and AD-type B patients, respectively, with a sensitivity of 100.0% and a specificity of 81.7% for AD-type A. In patients with chest pain and D-dimer tests, the DLM could predict more precisely, achieving a positive predictive value of 62.5% in the prospective evaluation. Conclusions DLMs may serve as decision-supporting tools for AD identification and facilitate differential diagnosis in patients with acute chest pain.

BACKGROUND: Delayed diagnosis or misdiagnosis of acute myocardial infarction (AMI) is not unusual in daily practice. Since a 12-lead electrocardiogram (ECG) is crucial for the detection of AMI, a systematic algorithm to strengthen ECG interpretation may have important implications for improving diagnosis. AIMS: We aimed to develop a deep learning model (DLM) as a diagnostic support tool based on a 12-lead electrocardiogram. METHODS: This retrospective cohort study included 1,051/697 ECGs from 737/287 coronary angiogram (CAG)-validated STEMI/NSTEMI patients and 140,336 ECGs from 76,775 non-AMI patients at the emergency department. The DLM was trained and validated in 80% and 20% of these ECGs. A human-machine competition was conducted. The area under the receiver operating characteristic curve (AUC), sensitivity, and specificity were used to evaluate the performance of the DLM. RESULTS: The AUC of the DLM for STEMI detection was 0.976 in the human-machine competition, which was significantly better than that of the best physicians. Furthermore, the DLM independently demonstrated sufficient diagnostic capacity for STEMI detection (AUC=0.997; sensitivity, 98.4%; specificity, 96.9%). Regarding NSTEMI detection, the AUC of the combined DLM and conventional cardiac troponin I (cTnI) increased to 0.978, which was better than that of either the DLM (0.877) or cTnI (0.950). CONCLUSIONS: The DLM may serve as a timely, objective and precise diagnostic decision support tool to assist emergency medical system-based networks and frontline physicians in detecting AMI and subsequently initiating reperfusion therapy.

BACKGROUND: Accumulated experience and advances in device technology have led to the increasing off-label use of transcatheter aortic valve replacement (TAVR) for pure native aortic valve regurgitation (PNAR). This study aimed to evaluate the procedural and long-term outcomes of using newer-generation transcatheter heart valves (THVs) versus early-generation self-expanding CoreValve (Medtronic, Minneapolis, USA) to treat PNAR. METHODS: TAVRs were performed with the use of early- (N=15) and newer-generation (N=10) THVs in a total of 25 consecutive PNAR patients at an intermediate-to-high risk for surgical aortic valve replacement [mean Society of Thoracic Surgeons (STS) score of 6.8±4.5]. Procedural and clinical outcomes were reported according to the Valve Academic Research Consortium 2 criteria. The primary end-point of the study was all-cause mortality, myocardial infarction (MI), disabling stroke, and readmission due to heart failure. RESULTS: The device success rate of the newer-generation THVs was significantly higher than that of the early-generation CoreValve (100% vs. 33%, P

Computed tomography (CT)-determined skeletal muscle measures have been used for predicting postoperative outcomes in patients undergoing transcatheter aortic valve implantation (TAVI). We investigated the impact of CT-determined muscle quantity (measured as psoas muscle area [PMA] and psoas muscle index [PMI]) and quality (measured as psoas muscle density [PMD]) on hospital length of stay (LOS) after TAVI.We retrospectively identified 182 consecutive patients who underwent TAVI between March 2013 and August 2017 with adequate preprocedural CT imaging. Baseline demographic and clinical data, the Society of Thoracic Surgeons score, the essential frailty toolset (EFT) frailty rating, and precontrast PMD, PMA, and PMI were obtained in all study patients. The primary outcome was prolonged postoperative LOS defined as greater than 14 days.Patients with prolonged LOS had a significantly higher Society of Thoracic Surgeons score (p0.001) and significantly lower PMD (p0.001) than those with LOS ≤14 days. More patients with prolonged LOS had concomitant peripheral vascular disease (p = 0.001), had undergone percutaneous coronary interventions (p = 0.022), and had an EFT score ≥4 (p0.001) compared to those without prolonged LOS. Neither PMA (p = 0.123) nor PMI (p = 0.271) were associated with prolonged LOS. Multivariate analysis identified EFT score ≥4, the presence of peripheral vascular disease, and PMD as independent predictors of prolonged LOS.The precontrast CT-determined muscle quality measurement PMD is a simple and objective predictor of prolonged LOS after TAVI.

(1) Background: While an artificial intelligence (AI)-based, cardiologist-level, deep-learning model for detecting acute myocardial infarction (AMI), based on a 12-lead electrocardiogram (ECG), has been established to have extraordinary capabilities, its real-world performance and clinical applications are currently unknown. (2) Methods and Results: To set up an artificial intelligence-based alarm strategy (AI-S) for detecting AMI, we assembled a strategy development cohort including 25,002 visits from August 2019 to April 2020 and a prospective validation cohort including 14,296 visits from May to August 2020 at an emergency department. The components of AI-S consisted of chest pain symptoms, a 12-lead ECG, and high-sensitivity troponin I. The primary endpoint was to assess the performance of AI-S in the prospective validation cohort by evaluating F-measure, precision, and recall. The secondary endpoint was to evaluate the impact on door-to-balloon (DtoB) time before and after AI-S implementation in STEMI patients treated with primary percutaneous coronary intervention (PPCI). Patients with STEMI were alerted precisely by AI-S (F-measure = 0.932, precision of 93.2%, recall of 93.2%). Strikingly, in comparison with pre-AI-S (N = 57) and post-AI-S (N = 32) implantation in STEMI protocol, the median ECG-to-cardiac catheterization laboratory activation (EtoCCLA) time was significantly reduced from 6.0 (IQR, 5.0–8.0 min) to 4.0 min (IQR, 3.0–5.0 min) (p &lt, 0.01). The median DtoB time was shortened from 69 (IQR, 61.0–82.0 min) to 61 min (IQR, 56.8–73.2 min) (p = 0.037). (3) Conclusions: AI-S offers front-line physicians a timely and reliable diagnostic decision-support system, thereby significantly reducing EtoCCLA and DtoB time, and facilitating the PPCI process. Nevertheless, large-scale, multi-institute, prospective, or randomized control studies are necessary to further confirm its real-world performance.

The outcomes of treating coronary artery disease (CAD) in very small vessels2.25 mm are sparse. The present study aimed to compare the safety and efficacy of the Resolute Onyx 2.0 mm drug-eluting stent (DES) (Medtronic) with the Onyx 2.25 mm DES for the treatment of CAD.We retrospectively evaluated patients who underwent percutaneous coronary intervention (PCI) for CAD involving Onyx 2.0 mm DES (Onyx 2.0 group) and Onyx 2.25 mm DES (Onyx 2.25 group) in the 2 consecutive years from November 2016 to November 2018. Major adverse cardiac and cerebral event (MACCE) rate, defined as all-cause mortality, non-fatal myocardial infarction, stroke, and repeat revascularization for target-lesion failure, was reported.A total of 152 subjects with 160 lesions were enrolled. The baseline demographics, lesion characteristics, and procedural results between the two groups were similar. The lesions were significantly shorter (P.01), fewer stents were consequently deployed (P=.04), and the total stent length was shorter (P.01) in the Onyx 2.0 group vs the Onyx 2.25 group. At a median follow-up of 673 days, MACCE rate did not differ significantly between the two groups. Multivariate analysis identified the presence of atrial fibrillation, chronic kidney disease, and the use of statins to be independently associated with MACCE.Our data suggest that the use of the Onyx 2.0 mm DES to treat CAD in very small vessels (2.25 mm) is feasible and safe, and the clinical outcomes were similar to those of the Onyx 2.25 mm group.

Statins constitute the mainstay treatment for atherosclerotic cardiovascular disease, which is associated with the risk of new-onset diabetes mellitus (NODM). However, the effects of individual statins on the risk of NODM remain unclear. We recruited 48,941 patients taking one of the three interested statins in a tertiary hospital between 2006 and 2018. Among them, 8337 non-diabetic patients taking moderate-intensity statins (2 mg/day pitavastatin, 10 mg/day atorvastatin, and 10 mg/day rosuvastatin) were included. The pitavastatin group had a higher probability of being NODM-free than the atorvastatin and rosuvastatin groups during the 4-year follow-up (log-rank test: p = 0.038). A subgroup analysis revealed that rosuvastatin had a significantly higher risk of NODM than pitavastatin among patients with coronary artery disease (CAD) (adjusted HR [aHR], 1.47, 95% confidence interval [CI], 1.05&ndash, 2.05, p = 0.025), hypertension (aHR, 1.26, 95% CI, 1.00&ndash, 1.59, p = 0.047), or chronic obstructive pulmonary disease (COPD) (aHR, 1.74, 95% CI, 1.02&ndash, 2.94, p = 0.04). We concluded that compared with rosuvastatin, reduced diabetogenic effects of pitavastatin were observed among patients treated with moderate-intensity statin who had hypertension, COPD, or CAD. Additional studies are required to prove the effects of different statins on the risk of NODM.

BackgroundThe initial detection and diagnosis of ST-segment or non-ST-segment elevation myocardial infarction (STEMI or NSTEMI) definitely rely on a 12-lead electrocardiogram (ECG). Delay or misdiagnosis is not unusual by subjective interpretation. Our aim is to develop a DLM as a diagnostic support tool to detect MI based on a 12-lead ECG and to evaluate the performance of this model.MethodsThis study included 1,051 ECGs from 737 coronary angiography (CAG)-validated STEMI patients, 697 ECGs from 287 CAG-validated NSTEMI patients, and 140,336 not-MI ECGs from 76,775 patients at emergency departments. DLM was trained and validated for the performance using 80% and 20% of the ECGs, respectively. A human-machine competition was conducted. The area under the receiver operating characteristic curve (AUC), sensitivity, and specificity were used to evaluate the performance of DLM and experts. STEMI versus not-STEMI, and MI versus not-MI were evaluated by DLM.ResultsThe AUCs of DLM for identifying STEMI and MI were 0.976 and 0.944 in the human-machine competition, respectively, which were significantly better than those of our best clinicians. In the real world setting, DLM presented with AUC of 0.995/0.916 with corresponding sensitivities of 96.9%/77.0%, and specificities of 96.2%/92.9% in the identification of STEMI and MI, respectively. Furthermore, DLM demonstrated sufficient diagnostic capacity for STEMI without the aid of troponin I (TnI) (AUC= 0.996) with corresponding sensitivity and specificity of 98.4% and 96.9%. The AUC of combined DLM and the first recorded TnI for the detection of NSTEMI were increased to 0.978 with corresponding sensitivity and specificity of 91.6% and 96.7%, which was better than that of DLM (0.877) or TnI (0.949) alone. ConclusionsDLM may serve as a diagnostic decision tool to assist intensive or emergency medical system-based networks and frontline physicians in identifying STEMI and NSTEMI in a timely and precise manner to prevent delay or misdiagnosis, and thereby to facilitate subsequent reperfusion therapy.

Data on whether different transcatheter aortic valve replacement (TAVR) devices and delivery approaches can achieve equally favorable outcomes when performed by a single heart team are scarce. We sought to compare the performance and short-term outcomes of three different TAVR devices-self-expanding Medtronic CoreValve (MCV), mechanically expanded Lotus valve, and balloon-expandable Edwards SAPIEN XT (SXT)-for the treatment of severe aortic stenosis (AS) in a single large-volume center in Taiwan.We retrospectively reviewed consecutive patients who underwent TAVR for the treatment of severe AS. Clinical outcomes were reported following Valve Academic Research Consortium 2 (VARC-2) criteria. The composite primary endpoint was combined all-cause mortality, myocardial infarction (MI), or disabling stroke within 180 days.A total of 231 patients (MCV n=112, Lotus n=18, and SXT n=101) were included. The device and procedural success rates were similar among all three TAVR devices. At 30 days, there was no significant difference in all-cause mortality, cardiovascular mortality, periprocedural MI, stroke, major vascular complications, life-threatening bleeding, acute kidney injury (AKI, stage 2/3), or VARC-2 composite early safety endpoints. There was no difference among groups in the rate of primary endpoint within 180 days. Lack of procedural success, presence of acute coronary occlusion during TAVR, and presence of AKI (stage 3) after TAVR were independent predictors of adverse outcomes.TAVR using MCV, Lotus, or SXT was associated with similar 30- and 180-day clinical outcomes. The presence of periprocedural complications was one of the main determinants of short-term adverse outcomes.

BACKGROUND AND PURPOSE: Atherosclerosis, resulting from lipid dysregulation and vascular inflammation, causes atherosclerotic cardiovascular disease (ASCVD), which contributes to morbidity and mortality worldwide. Chalcone and its derivatives possess beneficial properties, including anti‐inflammatory, antioxidant and antitumour activity with unknown cardioprotective effects. We aimed to develop an effective chalcone derivative with antiatherogenic potential. EXPERIMENTAL APPROACH: Human THP‐1 cells and HUVECs were used as in vitro models. Western blots and real‐time PCRs were performed to quantify protein, mRNA and miRNA expressions. The cholesterol efflux capacity was assayed by (3)H labelling of cholesterol. LDL receptor knockout (Ldlr (−/−)) mice fed a high‐fat diet were used as an in vivo atherogenesis model. Haematoxylin and eosin and oil red O staining were used to analyse plaque formation. KEY RESULTS: Using ATP‐binding cassette transporter A1 (ABCA1) expression we identified the chalcone derivative, 1m‐6, which enhances ABCA1 expression and promotes cholesterol efflux in THP‐1 macrophages. Moreover, 1m‐6 stabilizes ABCA1 mRNA and suppresses the expression of potential ABCA1‐regulating miRNAs through nuclear factor erythroid 2‐related factor 2 (Nrf2)/haem oxygenase‐1 (HO‐1) signalling. Additionally, 1m‐6 significantly inhibits TNF‐α‐induced expression of adhesion molecules, vascular cell adhesion molecule 1 (VCAM‐1) and intercellular adhesion molecule 1 (ICAM‐1), plus production of proinflammatory cytokines via inhibition of JAK/STAT3 activation and the modulation of Nrf2/HO‐1 signalling in HUVECs. In atherosclerosis‐prone mice, 1m‐6 significantly reduces lipid accumulation and atherosclerotic plaque formation. CONCLUSION AND IMPLICATIONS: Our study demonstrates that 1m‐6 produces promising atheroprotective effects by enhancing cholesterol efflux and suppressing inflammation‐induced endothelial dysfunction, which opens a new avenue for treating ASCVD. LINKED ARTICLES: This article is part of a themed issue on Risk factors, comorbidities, and comedications in cardioprotection. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.23/issuetoc

Background: In the era of drug-eluting stents, although bare-metal stent (BMS) remains an option for percutaneous coronary intervention (PCI), restenosis remains the Achilles' heel of BMS implantation. A recent study demonstrated several pleiotropic anti-inflammatory effects of dextromethorphan (DXM). This study aims to evaluate the effects of DXM on the outcome of PCI with BMS implantation. Methods: In this prospective, double-blind, randomized trial, we enrolled 55 patients who underwent PCI with BMS implantation from May 2006 to February 2009. The patients were divided into DXM (60 mg once daily) and placebo groups. We compared mortality rates, myocardial infarction (MI), target lesion revascularization (TLR), restenosis, stent thrombosis, and plasma levels of high-sensitivity C-reactive protein (hs-CRP) with repeated coronary angiography 6 months after the initial procedure. Results: During the 6-month follow-up period, no events of death, MI and stent thrombosis were reported in both groups. The TLR rate was 16.7% in patients receiving DXM compared to 24% receiving a placebo (P = 0.521). The restenosis rate was 30% in patients receiving DXM as compared to 40% receiving the placebo (P = 0.571). Although nonsignificant, the percentage of hs-CRP elevation was lower in the DXM group (20%) compared to the placebo group 32%; P = 0.363). Conclusions: DXM is safe to use in patients who underwent PCI. Although DXM therapy following BMS implantation did not significantly reduce the TLR and restenosis rates, it implied a trend toward a lower TLR and restenosis and reduced inflammation in the DXM group compared to the placebo group. Nonetheless, further extensive studies are warranted to elucidate the anti-restenosis effects of DXM.

Although digoxin is important in heart rate control, the utilization of digoxin is declining due to its narrow therapeutic window. Misdiagnosis or delayed diagnosis of digoxin toxicity is common due to the lack of awareness and the time-consuming laboratory work that is involved. Electrocardiography (ECG) may be able to detect potential digoxin toxicity based on characteristic presentations. Our study attempted to develop a deep learning model to detect digoxin toxicity based on ECG manifestations. This study included 61 ECGs from patients with digoxin toxicity and 177,066 ECGs from patients in the emergency room from November 2011 to February 2019. The deep learning algorithm was trained using approximately 80% of ECGs. The other 20% of ECGs were used to validate the performance of the Artificial Intelligence (AI) system and to conduct a human-machine competition. Area under the receiver operating characteristic curve (AUC), sensitivity, and specificity were used to evaluate the performance of ECG interpretation between humans and our deep learning system. The AUCs of our deep learning system for identifying digoxin toxicity were 0.912 and 0.929 in the validation cohort and the human-machine competition, respectively, which reached 84.6% of sensitivity and 94.6% of specificity. Interestingly, the deep learning system using only lead I (AUC = 0.960) was not worse than using complete 12 leads (0.912). Stratified analysis showed that our deep learning system was more applicable to patients with heart failure (HF) and without atrial fibrillation (AF) than those without HF and with AF. Our ECG-based deep learning system provides a high-accuracy, economical, rapid, and accessible way to detect digoxin toxicity, which can be applied as a promising decision supportive system for diagnosing digoxin toxicity in clinical practice.

BACKGROUND: Transcatheter aortic valve-in-valve implantation (aVIV) has been used to treat bioprosthetic failure due to "stent creep", defined as inward flexion or bending of stent posts. The aim of this study was to develop quantitative three-dimensional transesophageal echocardiography (3D-TEE) geometric analysis of failed bioprostheses to determine the incidence of stent creep in patients undergoing aVIV and its contribution to the hemodynamics of those valves. METHODS: We retrospectively examined the 3D-TEE of 22 consecutive patients (age 74.4 ± 11.3 years; M/F = 12/10) who underwent aVIV for failed bioprostheses. The modes of bioprosthesis failure included stenosis (n = 8), regurgitation (n = 9), and combined (n = 5). The degree of stent creep was assessed by calculating the triangular area obtained by projecting the apex of stent posts on a reconstructed plane. This measured area was divided by that of the regular triangle defined by the base of stent posts to calculate a ratio, which we termed the "stent creep ratio" (SCR). RESULTS: The mean SCR was lower in the patients with failed prostheses than that in the controls (0.82 ± 0.16 vs. 0.96 ± 0.05, p = 0.02). The SCR was negatively correlated with the peak trans-aortic pressure gradient (r = -0.62, p < 0.01). An SCR cut-off point of 0.79 was associated with aortic peak velocity > 4 m/s (AUC = 0.81, sensitivity = 0.79, specificity = 0.83). Fourteen of the 22 patients had pre- and post-aVIV 3D-TEE, and the SCR was corrected satisfactorily from 0.81 ± 0.13 to 1.04 ± 0.19 (p < 0.01). CONCLUSIONS: SCR measured by 3D-TEE is feasible to quantitatively evaluate stent creep. Stent creep is an important mode of structural deterioration in surgical bioprostheses, which can be treated by aVIV.

Patient Initials or Identifier Number SDFL ### Relevant Clinical History and Physical Exam A 78-year-old lady was admitted to another hospital due to acute non-ST-elevation myocardial infarction 9 days ago. She underwent coronary angiography that showed calcified left main with the triple

Previous studies have shown that the use of fractional flow reserve (FFR) in addition to angiography significantly reduced the rate of all major adverse cardiovascular events (MACE). However, this practice has not been widely accepted and limited outcome data exist about FFR-guided percutaneous coronary intervention (PCI) in Taiwan. The aim of the present study was to evaluate the possible impact of FFR-guided PCI in coronary stenoses of intermediate severity.We performed a retrospective case-control study on 443 cases of intermediate coronary stenoses in 206 patients recruited from our computerized database. The study patients were divided into two groups: the FFR group (n = 101) and the angiography group (n = 105), matched with age, gender, clinical and angiographic lesion characteristics. In the angiography group, the indicated lesions had been treated with PCI by angiographic or anatomical assessment, whereas those patients in the FFR group underwent PCI of indicated lesions only if the FFR was0.80. The primary end point was the MACE rate regarding death, nonfatal myocardial infarction (MI), and target vessel failure at a mean follow-up of 418 days.The MACE rate was similar in both groups (6% in the angiography group and 3% in the FFR group, p = 0.06). However, FFR-guided PCI strategy prevented unnecessary revascularization in up to 75% of patients, and markedly reduced costs of the index hospitalization. Moreover, multivariate analysis found that the use of drug-eluting stent and statin therapy, and the presence of family history of premature coronary artery disease and periprocedural MI are independent predictors of clinical outcomes.FFR-guided intervention, compared to angiography-guided intervention for Taiwanese patients with coronary stenoses of intermediate severity, achieved similar clinical outcomes and provided cost-savings.

Background: Early fluid resuscitation is a key aspect in the successful management of critically ill patients, but the optimal goal for volume control after the acute stage of critical illness remains unclear. This study aimed to evaluate the prognostic value of bioimpedance spectrometry for fluid management in critically ill patients. Methods: In this prospective observational study, patients who consented to participate were screened within the first 24 hours of admission to a medical intensive care unit (ICU) from February 4, 2015, to January 31, 2016. Information on demographics, comorbidities, primary reasons for admission, baseline laboratory data, and ventilator or inotropic use were documented. Data of fluid intake, fluid output, and body weight were recorded for the first 3 days of ICU admission. Bioimpedance spectrometry was performed on the first and third days after ICU admission. All participants were followed until death or hospital discharge. Results: Of the 140 enrolled patients (median age: 70 years, interquartile range: 60-77 years), 23 (16.4%) patients died during hospitalization. Independent predictors of hospital mortality were Acute Physiology and Chronic Health Evaluation II scores (per 1 point increase, odds ratio [OR]: 1.101) and overhydration (OH) volume on the first day (per 1 L increase, OR: 1.216). Compared to normal OH status (OH volume between −1 and 1 L), hyper OH status (OH volume < −1 L) on the third day after ICU admission was an independent predictor of hospital death (OR: 7.609). Normal OH status on the third day was associated with greater numbers of ICU-free and ventilator-free days. Conclusion: Bioimpedance spectrometry can be used to predict outcomes in critically ill patients. Increased OH volume on day 1 and hyper OH volume on day 3 of ICU admission are associated with a greater risk of hospital mortality. Volume status on day 3 is associated with durations of ventilator use and ICU stay.

Patient Initials or Identifier Number A968081 ### Relevant Clinical History and Physical Exam The 76 y/o male is a patient with (1) Type 2 DM, (2) Hyperlipidemia, (3)Old CVA He suffered from dizziness, especially on exertion for several months. Carotid MRA, which was arranged, showed 67%

Background Although radial access for drug-eluting stent (DES) combined with rotational atherectomy (RA) in patients with calcified coronary lesions may be associated with a lower risk of major bleeding complications and obtain favorable clinical results compared with femoral access, the long-term outcome data of this approach were limited in contemporary DES era. Methods & Results This retrospective study sought to compare in-hospital and long-term outcomes for patients undergoing RA via the transradial (TR) and transfemoral (TF) route in 126 consecutive patients (59 radial, 67 femoral) from 2009 to 2014. TR RA procedures were performed in 44/62 (71%) by the three TR operators, compared with 15/64 (23%) by the four TF operators in the present study. Significantly smaller diameter guide catheters and burrs (1.39 ± 0.16 mm vs. 1.53 ± 0.24 mm, P = 0.001) were used in the TR group. Procedural success rates were similar in both TR and TF groups. There was a significantly less major access site bleeding complications in favor of radial artery access (2% vs. 16%, P = 0.012). The incidence of in-hospital death or myocardial infarction was low in both groups. Although a trend of lower adverse event rate was demonstrated in the TR group compared with the TF one, no statistical significance (21% vs. 27%, P = 0.135) was detected. Conclusions Radial access, a useful alternative to femoral access for RA and DES, can be safely and successfully performed on up to 71% of the patients with heavily calcified coronary lesions needing RA by experienced TR operators.

It has been well documented that although homozygosity of the variant aldehyde dehydrogenese-2 (ALDH2) gene allele, ALDH2*2, in Asians almost fully protects against alcoholism, the heterozygosity only affords a partial protection to varying degrees. The partial protection against alcoholism has been ascribed to the faster elimination of acetaldehyde by residual hepatic ALDH2 activity and the lower accumulation in circulation in nonalcoholic heterozygotes. The physiological basis for overcoming the protection in ALDH2*1/*2 alcoholics, however, remains unclear.To address this question, we recruited a total of 27 Han Chinese alcohol-dependent men, matched by age and body mass index, controlled for normal liver and cardiovascular functions, from a population base of 221 alcoholics. The participants were divided into ALDH2*1/*1 homozygotes (n = 13) and ALDH2*1/*2 heterozygotes (n = 14). After a moderate dose of ethanol (0.5 g/kg body weight), blood ethanol/acetaldehyde/acetate concentrations, cardiac and extracranial/intracranial arterial hemodynamic parameters, as well as self-rated subjective sensations, were measured for 130 min.ALDH2*1/*2 alcoholics exhibited significantly higher blood acetaldehyde levels as well as prominent cardiovascular effects and the subjective perceptions, compared with the ALDH2*1/*1 alcoholics. Comparable profiles of blood acetaldehyde were found between heterozygotic alcoholics and the previously reported nonalcoholic heterozygotes intaking the same dose of ethanol. ALDH2*1/*2 alcoholics revealed, however, significantly lower intensities in both physiologic and psychologic responses than did the nonalcoholic heterozygotes.These results indicate that acetaldehyde, rather than ethanol or acetate, is primarily responsible for the observed alcohol sensitivity reactions in heterozygotic alcoholics and suggest that physiological tolerance and/or innate low sensitivity may play a crucial role in overcoming the deterring response. A potential pharmacogenetic classification of acetaldehydism and alcoholism for alcoholics carrying the different ALDH2 genotypes is proposed.

Purpose It was unknown whether Ginkgo biloba extract has regulatory effects on human T lymphocytes activated by tissue necrosis factor-alpha (TNF- α ), which has an important role on the progression of inflammatory atherosclerotic plaques. We evaluated the effects of G. biloba extract on activated human peripheral T lymphocytes, which were isolated from human whole blood. Methods The human T lymphocytes were treated with 25–100 μg G. biloba extract for 2 h first. Then they were activated by TNF- α and H 2 O 2 to investigate the modulatory effects of G. biloba extract on human T lymphocytes. Electrophoretic mobility shift assay, Western blot (Immunoblot) analysis and immunoprecipitation kinase assays were used. Results The inhibition of activated human T lymphocyte specifically correlated with the down-regulation of AP-1 DNA-binding activities. G. biloba extract was unique in its ability to inhibit the activation of c-Jun NH 2 -terminal protein kinase. Conclusions G. biloba extract might have its novel therapeutic effects on inflammation-based atherosclerotic diseases.

It has been well documented that although homozygosity of the variant aldehyde dehydrogenase-2 (ALDH2) gene allele, ALDH2*2, in Asians almost fully protects against alcoholism, the heterozygosity only affords a partial protection to varying degrees. The full protection against alcoholism has been ascribed to the low-amount of alcohol hypersensitivity accompanied by a prolonged and large accumulation of acetaldehyde in blood (Peng et al. Pharmacogenetics 1999; 9:463-476). The physiological basis for the partial protection, however, remains unclear.To address this question, we recruited a total of 32 adult Han Chinese men, matched by age, body-mass index, and nutritional state from a population base of 404 men. The subjects were divided into 3 combinatorial genotypic groups of alcohol dehydrogenase (ADH) and ALDH, that is, ALDH2*1/*1-ADH1B*1/*1-ADH1C*1/*1 (n=8), ALDH2*1/*1-ADH1B*2/*2-ADH1C*1/*1 (n=8), and ALDH2*1/*2-ADH1B*2/*2-ADH1C*1/*1 (n=16). Following a moderate dose of ethanol (0.5 g/kg body weight), blood ethanol/acetaldehyde/acetate concentrations, cardiac and extracranial/intracranial arterial hemodynamic parameters, as well as self-rated subjective sensations, were measured for 130 min.Heterozygotic ALDH2*1/*2 subjects were found to be strikingly responsive to the moderate amount of alcohol, as evidenced by the prominent cardiovascular effects as well as subjective perceptions of general discomfort for as long as 2 h following ingestion. The ADH1B polymorphisms did not appear to correlate with the pharmacokinetic and pharmacodynamic effects.These results indicate that acetaldehyde, rather than ethanol or acetate, is primarily responsible for the observed alcohol sensitivity reactions and suggest that substantially lower accumulation of blood acetaldehyde in the heterozygotes significantly reduces the aversion reaction to low amounts of alcohol that permits other biological as well as environmental factors to facilitate drinking and the according risk for the disease.

1 Irbesartan is a promising antihypertensive drug with beneficial effects on atherosclerotic processes. In the progression of atherosclerosis, human T-lymphocytes play an important role, but it is not yet known how irbesartan modulates human T-lymphocytes activation. To gain insight into the mechanisms by which irbesartan acts, we investigated its effects on human T-lymphocytes. 2 Primary human T-lymphocytes were isolated from whole blood. Cytokines were determined by ELISA. Activator protein-1 (AP-1) and related protein activities were determined by electrophoretic mobility shift assays, kinase assays, Western blotting and transfection assays. 3 Irbesartan inhibited the production of both tumor necrosis factor-alpha and interferon-gamma by activated T-cells, especially at therapeutic concentrations. Further investigation at the molecular level indicated that the inhibition of activated human T-lymphocytes specifically correlated with the downregulation of AP-1 DNA-binding activity. In the Jurkat T-cell line, irbesartan also inhibited AP-1 transcriptional activity. Finally, we revealed that irbesartan is unique in its ability to inhibit the activation of both c-Jun NH2-terminal protein kinase and p38 MAPK. 4 Our studies show that irbesartan may modulate inflammation-based atherosclerotic diseases through a cell-mediated mechanism involving suppression of human T-lymphocytes activation via downregulation of AP-1 activity.

Chronic inflammation is one of the important mechanisms involved in atherosclerosis formation. The activated monocytes and their secreted cytokines contribute significantly to this inflammatory process. Here we examined the effects of carvedilol, a recently introduced cardio-protective alpha-1- and beta-receptor blocker, on cytokine production from various stimuli-activated human immune effector cells. By ELISA analysis, we showed that carvedilol inhibited interferon-gamma (IFN-gamma), but enhanced interleukin (IL)-12 production in phytohemagglutinin (PHA)- and concanavalin A (ConA)-stimulated human peripheral blood mononuclear cells (PBMCs). The production of tumor necrosis factor-alpha (TNF-alpha) was marginally affected. When purified monocytes were examined, we observed the consistent up-regulation of IL-12 production while both IL-10 and TNF-alpha were unaffected or marginally down-regulated, respectively, by carvedilol. In agreement with the observation in monocytes, the production of IL-12 from activated macrophages was also up-regulated by carvedilol. We concluded that carvedilol might mediate its therapeutic effects through differentially regulating cytokine production from activated mononuclear cells, including at least monocytes and macrophages.

The activation of T lymphocytes contributes to inflammatory process of cardiovascular and cerebrovascular diseases. We investigated the effects of the extract of Ginkgo biloba (EGb), an ancient plant preserving antioxidant property, on phorbol 12-myristate 13-acetate+ionomycin or anti-CD3+anti-CD28 monoclonal antibodies-activated T cells. Human peripheral blood T cells were negatively selected from whole blood. Cytokines were measured by ELISA, cell surface markers by flow cytometry and the activities of transcription factors and kinases were determined by electrophoresis mobility shift assays, kinase assays and transfection assays. We showed that EGb inhibited several cytokines, including tumor necrosis factor-alpha, interleukin (IL)-2, IL-4 and interferon-gamma production from activated T cells. Electrophoresis mobility shift assay analysis indicated that EGb down-regulated activator protein-1 (AP-1) but not nuclear factor kappa B DNA-binding activity. In addition, EGb inhibited c-jun N-terminal kinase but not extracellular signal regulated protein kinase activity. The inhibitory specificity on AP-1 by EGb was also demonstrated in transfection assays. The inhibition of AP-1 signaling pathway in T cells by EGb provides a support for its efficacy in cardiovascular and cerebrovascular diseases and raises a therapeutic potential for this drug in activated T cell-mediated pathologies.

Both granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-10 (IL-10) are important mediators regulating inflammatory responses. Inflammatory processes have an important role in atherogenesis. In this paper, the effects of carvedilol on GM-CSF-induced IL-10 production were examined on human monocytic cell line, U937, and purified human monocytes. First, we showed that one-time carvedilol pretreatment at concentrations 0.3-10 microM dose-dependently inhibited GM-CSF-induced IL-10 production in U937 cells. In addition, we found carvedilol to be non-cytotoxic at concentrations equal to or less than 10 microM. However, at concentrations higher than 10 microM, carvedilol induced programmed cell death in U937 cells. The inhibition of GM-CSF-induced IL-10 production by carvedilol was also observed at the expression of mRNA. Furthermore, the inhibition of IL-10 production was demonstrated in GM-CSF-activated purified human peripheral blood monocytes. Finally, long-term carvedilol pretreatment of U937 cells up to 2 months at concentrations of 1.0 microM mildly enhanced the IL-10 production. Our observations that carvedilol modulated GM-CSF-induced IL-10 production may have some implication in understanding the broad-spectrum effects of carvedilol in regulating inflammatory reactions.

Retrograde aortocoronary dissection is a rare but devastating complication of coronary angioplasty. It occurs most frequently in the right coronary artery, rarely in the left. This is a case report of an aortic dissection complicated by coronary angioplasty of the left circumflex artery. Stenting of the left main coronary artery successfully sealed the entry point of dissection.

A 53-year-old man experienced persistent chest pain followed by slight shortness of breath after being hit in the chest by a stranger. Chest X-ray study showed no rib fractures but electrocardiography indicated acute anterior wall myocardial infarction. Echocardiography revealed akinesia in both the interventricular septum and anterior left ventricular wall. Emergency cardiac catheterization demonstrated total occlusion of the proximal left anterior descending coronary artery, 9 h after the event. He was successfully treated with coronary angioplasty and stenting procedures. However, poor left ventricular function was observed 3 months after the event despite medications. We conclude that evaluation for possible myocardial injury should be considered soon after blunt chest trauma for early treatment to improve prognosis.

To compare the effect of intracoronary adenosine and isosorbide dinitrate (ISDN) on no-reflow/slow flow during high-speed rotational atherectomy (HSRA) in patients with complex coronary artery disease (CAD).Medical records from consecutive patients diagnosed with complex CAD between November 2002 and March 2006 who underwent HSRA at the Tri-Service General Hospital, National Defence Medical Centre in Taipei, Taiwan, were included in this study. Patients in the adenosine group (n=32) received a 50 microg intracoronary adenosine bolus prior to the initiation of burr rotation and during each ablation. Patients in the ISDN group (n=58) received a 0.5 mg intracoronary ISDN bolus at comparable time points. Angiographic success was achieved in 100% of patients in the adenosine group and 98.3% (57/58) in the ISDN group.The procedural success rates were 96.9% (31/32) in the adenosine group and 89.7% (52/58) in the ISDN group. One patient (3.1%) from the adenosine group and six patients (10.3%) from the ISDN group experienced no-reflow/slow flow (P = 0.414). No in-hospital mortality occurred and target vessel revascularization was unnecessary.Intracoronary administration of either adenosine or ISDN during HSRA appears safe and administration of either agent may be effective in decreasing the incidence of no-reflow/slow flow during HSRA. Further large, prospective, randomized, placebo-controlled trials are required.

Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are the principal enzymes responsible for metabolism of ethanol. Both ADH and ALDH exhibit genetic polymorphisms among racial populations. Functional variant alleles ADH1B*2 and ALDH2*2 have been consistently replicated to show protection against developing alcohol dependence. Multiple logistic regression analyses suggest that ADH1B*2 and ALDH2*2 may independently influence the risk for alcoholism. It has been well documented that homozygosity of ALDH2*2 almost fully protects against developing alcoholism and that the heterozygosity only affords a partial protection to varying degrees. Correlations of blood ethanol and acetaldehyde concentrations, cardiovascular hemodynamic responses, and subjective perceptions have been investigated in men with different combinatorial ADH1B and ALDH2 genotypes following challenge with ethanol for a period of 130 min. The pharmacokinetic and pharmacodynamic consequences indicate that acetaldehyde, rather than ethanol, is primarily responsible for the observed alcohol sensitivity reactions, suggesting that the full protection by ALDH2*2/*2 can be ascribed to the intense unpleasant physiological and psychological reactions caused by persistently elevated blood acetaldehyde after ingesting a small amount of alcohol and that the partial protection by ALDH2*1/*2 can be attributed to a faster elimination of acetaldehyde and the lower accumulation in circulation. ADH1B polymorphism does not significantly contribute to buildup of the blood acetaldehyde. Physiological tolerance or innate insensitivity to acetaldehyde may be crucial for development of alcohol dependence in alcoholics carrying ALDH2*2.

Statins are applied clinically to treat hypercholesterolemia and proposed to have some kinds of anti-inflammatory properties for reducing the incidence of atherosclerosis-related cardiovascular events. However, it was rarely known about statins on the signal transduction on human primary T cells. To gain insight into the mechanism of statins on human T cells, we investigated the effects of both lovastatin and atorvastatin on activated human primary T cells. The human primary T cells from the blood of normal human beings were isolated. We found that lovastatin, but not atorvastatin, can dose-dependently inhibit cytokine production such as interleukin-2, interleukin-4, and interferon-gamma from activated human T cells. Neither lovastatin nor atorvastatin can regulate the TNF-alpha production on both activated human T cells and monocytes. Molecular investigation was performed that lovastatin, but not atorvastatin, could down-regulate both activator protein-1 and NF-kappaB DNA binding activities, assessed by electrophoretic mobility shift assay. Our observations may extend potential and differential therapeutic mechanisms of lovastatin with cell-mediated capacity to prevent or treat some of inflammation related diseases.

1 Irbesartan is a promising antihypertensive drug with beneficial effects on atherosclerotic processes. In the progression of atherosclerosis, human T-lymphocytes play an important role, but it is not yet known how irbesartan modulates human T-lymphocytes activation. To gain insight into the mechanisms by which irbesartan acts, we investigated its effects on human T-lymphocytes. 2 Primary human T-lymphocytes were isolated from whole blood. Cytokines were determined by ELISA. Activator protein-1 (AP-1) and related protein activities were determined by electrophoretic mobility shift assays, kinase assays, Western blotting and transfection assays. 3 Irbesartan inhibited the production of both tumor necrosis factor-alpha and interferon-gamma by activated T-cells, especially at therapeutic concentrations. Further investigation at the molecular level indicated that the inhibition of activated human T-lymphocytes specifically correlated with the downregulation of AP-1 DNA-binding activity. In the Jurkat T-cell line, irbesartan also inhibited AP-1 transcriptional activity. Finally, we revealed that irbesartan is unique in its ability to inhibit the activation of both c-Jun NH2-terminal protein kinase and p38 MAPK. 4 Our studies show that irbesartan may modulate inflammation-based atherosclerotic diseases through a cell-mediated mechanism involving suppression of human T-lymphocytes activation via downregulation of AP-1 activity.