Predicting severe proximal left anterior descending coronary artery stenosis using proximal left anterior descending coronary artery tortuosity and the angle between the left main and anterior descending coronary arteries: a retrospective cross-sectional study.

Background: Coronary bifurcation angles influence plaque initiation in the coronary artery, and changes in blood flow caused by tortuosity in the coronary arteries can reduce blood pressure distal to the tortuous portion of the coronary artery, leading to myocardial ischemia. We aimed to describe two factors (coronary artery tortuosity and bifurcation angle) as one descriptor for the evaluation of proximal left anterior descending coronary artery (LAD) disease. Methods: We reviewed the medical records of 133 consecutive patients who underwent computed tomography angiography (CTA) for angina symptoms between November 2019 and January 2020. The patients were divided into two groups according to the presence of significant LAD stenosis on CTA (defined as LAD stenosis >50%). The straight length of the vessel was measured using the central luminal line of the flow path, and, calculated using proprietary algorithms in TeraRecon software. We used three-dimensional volume rendering and two-dimensional axial images to measure the left main coronary artery (LM)-LAD angles. Results: In the univariate analysis, there were significant differences in the linear distance between the endpoints of the 20 mm actual curve of the LAD (d20), cosine value for LM-LAD angle (cosθ) <0.8, age, presence of hypertension or diabetes, and number of pack years [hazard ratio (HR): 2.70, 8.04, 1.05, 3.70, 2.82, and 1.04; P=0.029, P<0.001, P=0.020, P=0.024, P=0.021, and P=0.002, respectively]. However, in the multivariate analysis, the cosθ multiplied by d20 (d20*cosθ) <15.5, presence of hypertension and number of pack years (HR: 11.36, 4.54, and 1.04; P<0.001, P=0.019, and P=0.003, respectively) were predictors of significant proximal LAD stenosis. Conclusions: As the tortuosity and LM-LAD angle increased (d20 and cosθ decreased, respectively), the chance of proximal LAD lesions formation increased. d20*cosθ might be useful as a predictor of proximal LAD stenosis.

Admixture of divergent genomes facilitates hybridization across species in the family Brassicaceae.

Hybridization and polyploidization are pivotal to plant evolution. Genetic crosses between distantly related species are rare in nature due to reproductive barriers but how such hurdles can be overcome is largely unknown. Here we report the hybrid genome structure of xBrassicoraphanus, a synthetic allotetraploid of Brassica rapa and Raphanus sativus. We performed cytogenetic analysis and de novo genome assembly to examine chromosome behaviors and genome integrity in the hybrid. Transcriptome analysis was conducted to investigate expression of duplicated genes in conjunction with epigenome analysis to address whether genome admixture entails epigenetic reconfiguration. Allotetraploid xBrassicoraphanus retains both parental chromosomes without genome rearrangement. Meiotic synapsis formation and chromosome exchange are avoided between nonhomologous progenitor chromosomes. Reconfiguration of transcription network occurs, and less divergent cis-elements of duplicated genes are associated with convergent expression. Genome-wide DNA methylation asymmetry between progenitors is largely maintained but, notably, B. rapa-originated transposable elements are transcriptionally silenced in xBrassicoraphanus through gain of DNA methylation. Our results demonstrate that hybrid genome stabilization and transcription compatibility necessitate epigenome landscape adjustment and rewiring of cis-trans interactions. Overall, this study suggests that a certain extent of genome divergence facilitates hybridization across species, which may explain the great diversification and expansion of angiosperms during evolution.

Serum microRNA-185 Levels and Myocardial Injury in Patients with Acute ST-segment Elevation Myocardial Infarction.

Objective Human microRNA-185 (miR-185) has been reported to act as a regulator of fibrosis and angiogenesis in cancer. However, miR-185 has not been investigated in patients with ST-segment elevation myocardial infarction (STEMI). We hypothesized that the changes in miR-185 levels in STEMI patients are related to the processes of myocardial healing and remodeling. Methods Between January 2011 and December 2013, 145 patients with STEMI (65.9±11.6 years old; 41 women) were enrolled. Initial and discharge serum samples collected from 20 patients with STEMI and mixed sera from 8 healthy controls were analyzed by a microarray. A quantitative reverse transcription polymerase chain reaction (RT-qPCR) analysis of miR-185 was performed in all 145 patients. The correlation between the miR-185 levels and the clinical, laboratory, angiographic, and echocardiographic parameters was analyzed. Results The microarray analysis revealed a biphasic pattern in miR-185 levels, with an initial decrease followed by an increase at discharge. The miR-185 levels at discharge were significantly correlated with the troponin-I, CK-MB, and area under the curve of CK-MB levels. There was a positive correlation between the transforming growth factor-ß and miR-185 levels at discharge (ρ=0.242, p=0.026). A high wall motion score index and a low ejection fraction, as measured by echocardiography, and high B-type natriuretic peptide level at one month after STEMI were related to high miR-185 levels. Conclusion Our results showed that elevated miR-185 levels at the late stage of STEMI were related to a large amount of myocardial injury and adverse remodeling.

Pharmacodynamic Profile and Prevalence of Bleeding Episode in East Asian Patients with Acute Coronary Syndromes Treated with Prasugrel Standard-Dose versus De-escalation Strategy: A Randomized A-MATCH Trial.

Compared with Caucasian patients, East Asian patients have the unique risk-benefit trade-off and different responsiveness to antithrombotic regimens. The aim of this study was to compare pharmacodynamic profile in East Asian patients with acute coronary syndromes (ACSs) treated with prasugrel standard-dose versus a de-escalation strategy. Before discharge, ACS patients with age <75 years or weight ≥60 kg (n = 255) were randomly assigned to the standard-dose (10-mg group) or de-escalation strategy (5-mg group or platelet function test [PFT]-guided group). After 1 month, VerifyNow P2Y12 assay-based platelet reactivity (P2Y12 reaction unit [PRU]) and bleeding episodes were evaluated. Primary endpoint was the percentage of patients with the therapeutic window (85 ≤ PRU ≤ 208). The 250 patients completed 1-month treatment. The percentage of patients within the therapeutic window was significantly lower in the 10-mg group (n = 85) compared with the 5-mg (n = 83) and PFT-guided groups (n = 82) (35.3 vs. 67.5 vs. 65.9%) (odds ratio [OR]: 3.80 and 3.54; 95% confidence interval [CI]: 2.01-7.21 and 1.87-6.69, respectively). Compared with the 10-mg group, the bleeding rate was tended to be lower with de-escalation strategies (35.3 vs. 24.1% vs. 23.2%) (hazard ratio [HR]: 0.58 and 0.55; 95% CI: 0.30-1.14 and 0.28-1.09, respectively). "PRU < 127" was the optimal cut-off for predicting 1-month bleeding events (area under the curve: 0.616; 95% CI: 0.543-0.689; p = 0.005), which criteria was significantly associated with early discontinuation of prasugrel treatment (HR: 2.00; 95% CI: 1.28-3.03; p = 0.001). In conclusion, compared with the standard-dose prasugrel, the prasugrel de-escalation strategy in East Asian patients presented with ACS showed a higher chance within the therapeutic window and a lower tendency toward bleeding episodes. REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier:NCT01951001.

Effect of Ticagrelor on Left Ventricular Remodeling in Patients With ST-Segment Elevation Myocardial Infarction (HEALING-AMI).

OBJECTIVES: The aim of this study was to evaluate the effect of ticagrelor versus clopidogrel on left ventricular (LV) remodeling after reperfusion of ST-segment elevation myocardial infarction (STEMI) in humans. BACKGROUND: Animal studies have demonstrated that ticagrelor compared with clopidogrel better protects myocardium against reperfusion injury and improves remodeling after myocardial infarction. METHODS: In this investigator-initiated, randomized, open-label, assessor-blinded trial performed at 10 centers in Korea, patients were enrolled if they had naive STEMI successfully treated with primary percutaneous coronary intervention (PCI) and at least 6-month planned duration of dual-antiplatelet treatment. The coprimary endpoints were LV remodeling index (LVRI) (a relative change of LV end-diastolic volume) measured on 3-dimensional echocardiography and N-terminal pro-B-type natriuretic peptide level at 6 months. RESULTS: Among initially enrolled patients with STEMI (n = 336), 139 in each group completed the study. LVRI at 6 months was numerically lower with ticagrelor versus clopidogrel (0.6 ± 18.6% vs. 4.5 ± 16.5%; p = 0.095). Ticagrelor significantly reduced the 6-month level of N-terminal pro-B-type natriuretic peptide (173 ± 141 pg/ml vs. 289 ± 585 pg/ml; p = 0.028). These differences were prominent in patients with pre-PCI TIMI (Thrombolysis In Myocardial Infarction) flow grade 0. By multivariate analysis, ticagrelor versus clopidogrel reduced the risk for positive LV remodeling (LVRI >0%) (odds ratio: 0.56; 95% confidence interval: 0.33 to 0.95; p = 0.030). The LV end-diastolic volume index remained unchanged during ticagrelor treatment (from 54.7 ± 12.2 to 54.2 ± 12.2 ml/m2; p = 0.629), but this value increased over time during clopidogrel treatment (from 54.6 ± 11.3 to 56.4 ± 13.9 ml/m2; p = 0.056) (difference -2.3 ml/m2; 95% confidence interval: -4.8 to 0.2 ml/m2; p = 0.073). Ticagrelor reduced LV end-systolic volume index (from 27.0 ± 8.5 to 24.7 ± 8.4 ml/m2; p < 0.001), whereas no reduction was seen with clopidogrel (from 26.2 ± 8.9 to 25.6 ± 11.0 ml/m2; p = 0.366) (difference -1.8 ml/m2; 95% confidence interval: -3.5 to -0.1 ml/m2; p = 0.040). CONCLUSIONS: Ticagrelor was superior to clopidogrel for LV remodeling after reperfusion of STEMI with primary PCI. (High Platelet Inhibition With Ticagrelor to Improve Left Ventricular Remodeling in Patients With ST Segment Elevation Myocardial Infarction [HEALING-AMI]; NCT02224534).

Clinical experience with distal transradial access for endovascular treatment of various noncoronary interventions in a multicenter study.

BACKGROUND: Transradial access is a well-known alternative to conventional transfemoral access for interventional procedures. Recently, transradial access through the "snuffbox", which lies in the radial dorsal aspect of the hand, has been introduced as a new technique with positional versatility. In this study, we aimed to evaluate the clinical feasibility and safety of distal transradial access for interventional procedures in a retrospective, multicenter study. MATERIAL & METHODS: Distal transradial access was attempted in 46 patients (36 men and 10 women; mean age, 64 years) who underwent 47 consecutive procedures from January 2018 to December 2019. Procedures included chemoembolization (19/47, 40.4%), bronchial artery embolization (7/47, 14.9%), renal intervention (3/47, 6.4%), arteriovenous fistula angioplasty (7/47, 14.9%), subclavian artery stenting (5/47, 10.6%), other embolization (5/47, 10.6%), and uterine artery embolization (1/47, 2.1%). We recorded the success rate of the procedures, complications, and postprocedural hemostasis time during the follow-up period. RESULTS: The technical success of distal transradial access without major complications was 97.9% (46/47). Of the 46 patients, one patient (2.2%) had a minor complication, which was a thrombotic segmental occlusion of the distal radial artery. Of the enrolled patients, only one patient did not complete the transradial access procedure via the snuffbox because the left proximal subclavian artery was occluded and a crossover to conventional transfemoral access was performed. The mean postprocedural hemostasis time was 131.7 minutes (range, 120-360 minutes). CONCLUSION: Distal transradial access can be a valid option for the endovascular treatment of various noncoronary interventions with technical feasibility and safety.

Head-to-head comparison of prognostic accuracy in patients undergoing noncardiac surgery of dobutamine stress echocardiography versus computed tomography coronary angiography (PANDA trial): A prospective observational study.

BACKGROUND: Dobutamine stress echocardiography (DSE) and coronary computed tomography angiography (CTA) can provide perioperative prognostic information in risk stratification of patients undergoing noncardiac surgery. This study directly compared the prognostic value of DSE and CTA in patients undergoing noncardiac surgery. METHODS: Between 2014 and 2016, 215 patients with more than one clinical risk factor for perioperative cardiovascular (CV) events were enrolled prospectively. They received both DSE and CTA before noncardiac surgery. Perioperative clinical risk was classified according to the revised cardiac risk index (RCRI), DSE results were categorized as abnormal (inducible ischemia and/or nonviable infarction) or not. CTA results were assessed using the severity of stenosis, with significant stenosis being ≥50% of the luminal diameter). After the exclusion, a total of 206 patients remained. Perioperative CV events were defined as CV death, non-fatal myocardial infarction (MI), myocardial injury, pulmonary edema, non-fatal stroke, and systemic embolism within 30 days after surgery. RESULTS: Twenty-four patients (12%) had perioperative cardiac events (1 cardiac death, 10 non-fatal MI, 8 myocardial injury, 11 pulmonary edema, 1 non-fatal stroke, and 1 pulmonary embolism). Following adjustment for baseline RCRI score, abnormal result on DSE (OR, 6.08, 95% CI, 2.41 to 15.31, P < 0.001), significant CAD on CTA (OR, 18.79; 95% CI, 5.24 to 67.42, P < 0.001), and high CACS (OR, 4.19; 95% CI, 1.39 to 12.60, P = 0.011) remained significant predictors of perioperative CV events. CONCLUSIONS: DSE and CTA are independent predictive factors of events in patients undergoing noncardiac surgery. Among them, assessment of significant CAD using CTA might show a higher prognostic value compared with DSE before noncardiac surgery. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02250963.

Individualized Follow-Up Strategy for Patients with an Indeterminate Response to Initial Therapy for Papillary Thyroid Carcinoma.

BACKGROUND: The concept of a dynamic risk-stratification scheme has been suggested for individualized management of patients with papillary thyroid carcinoma (PTC). However, there is no specified follow-up strategy for patients with an indeterminate response. METHODS: This study evaluated 403 PTC patients who had an indeterminate response during the first 12-24 months after initial therapy. All patients underwent total thyroidectomy with radioactive iodine remnant ablation. Patients were further classified into three groups based on risk of structural persistence/recurrence: a Tg+ group (detectable thyroglobulin [Tg], regardless of antithyroglobulin antibody [TgAb] or imaging findings; 196 patients), a TgAb+ group (positive results for TgAb with undetectable Tg, regardless of imaging findings; 46 patients), and an Image+ group (nonspecific findings on neck ultrasonography or faint uptake in the thyroid bed on whole-body scan, with undetectable Tg and negative results for TgAb; 161 patients). RESULTS: With a median of 9.6 years (interquartile range 7.7-11.2 years) of follow-up, 56 (14%) PTC patients had structural persistent/recurrent disease: 50 (89%) at locoregional sites and six (11%) at distant sites. The recurrence rate in Tg+, TgAb+, and Image + groups were 26.5%, 8.7%, and 0%, respectively. The median time to detection of structural persistent/recurrent disease from the initial thyroid surgery was 3.7 years (interquartile range 2.5-6.3 years). The optimal cutoff stimulated Tg level to predict structural persistent/recurrent disease was 3.1 ng/mL in the Tg+ group. This classification system revealed higher predictability of structural persistent/recurrent disease than the tumor-node-metastasis staging system and American Thyroid Association risk stratification (proportion of variation explained: 15.7% vs. 2.4% and 0.9%, respectively). Six (3%) patients with distant metastatic disease were all classified in the Tg+ group, and all had lung metastasis. CONCLUSIONS: The findings suggest a more individualized follow-up strategy for patients with an indeterminate response. More careful evaluation, including early evaluation of distant metastasis, is necessary in patients with elevated Tg levels. However, for patients testing positive for TgAb or those with only nonspecific imaging findings, regular follow-ups of Tg and TgAb levels and neck ultrasonography are sufficient.

Antiplatelet Therapy Combinations and Thrombogenicity in Patients with Non-Valvular Atrial Fibrillation.

BACKGROUND AND OBJECTIVES: Combination antiplatelet therapy reduces the risk of ischemic stroke compared with aspirin monotherapy in non-valvular atrial fibrillation (NVAF) patients. The underlying mechanism, however, remains unclear. In addition, the association between platelet inhibition and thrombogenicity in NVAF has not been evaluated. SUBJECTS AND METHODS: We randomized 60 patients with NVAF that were taking 100 mg of aspirin daily (>1 month) to adding 75 mg of clopidogrel daily (CLPD group), 100 mg of cilostazol twice daily (CILO group), or 1000 mg of omega-3 polyunsaturated fatty acid twice daily (PUFA group). Biomarkers (von Willebrand factor antigen [vWF:Ag], fibrinogen, D-dimer, and high-sensitivity C-reactive protein [hs-CRP]) and platelet reactivity (PR), which were the levels stimulated by adenosine diphosphate (ADP), thrombin-receptor agonist peptide, collagen, and arachidonic acid, were measured at baseline and 30-day follow-up. RESULTS: Combination antiplatelet therapy significantly reduced vWF:Ag and fibrinogen levels (7.7 IU/dL, p=0.015 and 15.7 mg/dL, p=0.005, respectively), but no changes were found in D-dimer and hs-CRP levels. The CLPD and CILO groups showed fibrinogen and vWF:Ag level reductions (24.9 mg/dL, p=0.015 and 9.3 IU/dL, p=0.044, respectively), whereas the PUFA group did not show any differences in biomarkers. Irrespective of regimen, the changes in fibrinogen and vWF:Ag levels were mainly associated with the change in ADP-mediated PR (r=0.339, p=0.008 and r=0.322, p=0.012, respectively). CONCLUSION: In patients with NVAF, combination antiplatelet therapy showed reductions for vWF:Ag and fibrinogen levels, which may be associated with the inhibitory levels of ADP-mediated PR. The clinical implications of these findings need to be evaluated in future trials.

Novel role of platelet reactivity in adverse left ventricular remodelling after ST-segment elevation myocardial infarction: The REMODELING Trial.

The role of platelet-leukocyte interaction in the infarct myocardium still remains unveiled. We aimed to determine the linkage of platelet activation to post-infarct left ventricular remodelling (LVR) process. REMODELING was a prospective, observational, cohort trial including patients (n = 150) with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention. Patients were given aspirin plus clopidogrel therapy (600 mg loading and 75 mg daily). Platelet reactivity (PRU: P2Y12 Reaction Units) was assessed with VerifyNow P2Y12 assay on admission. Transthoracic echocardiography was performed on admission and at one-month follow-up. The primary endpoint was the incidence of LVR according to PRU-based quartile distribution. LVR was defined as a relative ≥ 20 % increase in LV end-diastolic volume (LVEDV) between measurements. Adverse LVR was observed in 36 patients (24.0 %). According to PRU quartile, LVR rate was 10.8 % in the first, 23.1 % in the second, 27.0 % in the third, and 35.1 % in the fourth (p = 0.015): the optimal cut-off of PRU was ≥ 248 (area under curve: 0.643; 95 % confidence interval: 0.543 to 0.744; p = 0.010). LVR rate also increased proportionally according to the level of high sensitivity-C reactive protein (hs-CRP) (p = 0.012). In multivariate analysis, the combination of PRU (≥ 248) and hs-CRP (≥ 1.4 mg/l) significantly increased the predictive value for LVR occurrence by about 21-fold. In conclusion, enhanced levels of platelet activation and inflammation determined the incidence of adverse LVR after STEMI. Combining the measurements of these risk factors increased risk discrimination of LVR. The role of intensified antiplatelet or anti-inflammatory therapy in post-infarct LVR process deserves further study.

Coronary Microvascular Dysfunction as a Mechanism of Angina in Severe AS: Prospective Adenosine-Stress CMR Study.

BACKGROUND: Although a common symptom in patients with severe aortic stenosis (AS) without obstructive coronary artery disease (CAD), little is known about the pathogenesis of exertional angina. OBJECTIVES: This study sought to prove that microvascular dysfunction is responsible for chest pain in patients with severe AS and normal epicardial coronary arteries using adenosine-stress cardiac magnetic resonance (CMR) imaging. METHODS: Between June 2012 and April 2015, 117 patients with severe AS without obstructive CAD and 20 normal controls were enrolled prospectively. After exclusions, study patients were divided into 2 groups according to presence of exertional chest pain: an angina group (n = 43) and an asymptomatic group (n = 41), and the semiquantitative myocardial perfusion reserve index (MPRI) was calculated. RESULTS: MPRI values were significantly lower in severe AS patients than in normal controls (0.90 ± 0.31 vs. 1.25 ± 0.21; p < 0.001), and were much lower in the angina group than the asymptomatic group (0.74 ± 0.25 vs. 1.08 ± 0.28; p < 0.001). In logistic regression analysis, the only independent predictor for angina was MPRI (odds ratio: 0.003; p < 0.001). Univariate associations with MPRI were identified for diastolic blood pressure, E/e' ratio, left ventricular volume and ejection fraction, cardiac index, presence of late gadolinium enhancement, and left ventricular mass index (LVMI). In multivariate analysis, LVMI was the strongest contributing factor to MPRI (standardization coefficient: -0.428; p < 0.001). CONCLUSIONS: Our results suggest that, in patients with severe AS without obstructive CAD, angina is related to impaired coronary microvascular function along with LV hypertrophy detectable by semiquantitative MPRI using adenosine-stress CMR. CLINICAL TRIAL REGISTRATION: NCT02575768.

Effects of Peroxisome Proliferator-Activated Receptor-δ Agonist on Cardiac Healing after Myocardial Infarction.

Peroxisome proliferator-activated receptor-delta (PPAR-δ)-dependent signaling is associated with rapid wound healing in the skin. Here, we investigated the therapeutic effects of PPAR-δ-agonist treatment on cardiac healing in post-myocardial infarction (MI) rats. Animals were assigned to the following groups: sham-operated control group, left anterior descending coronary artery ligation (MI) group, or MI with administration of the PPAR-δ agonist GW610742 group. GW610742 (1 mg/kg) was administrated intraperitoneally after the operation and repeated every 3 days. Echocardiographic data showed no differences between the two groups in terms of cardiac function and remodeling until 4 weeks. However, the degrees of angiogenesis and fibrosis after MI were significantly higher in the GW610742-treated rats than in the untreated MI rats at 1 week following MI, which changes were not different at 2 weeks after MI. Naturally, PPAR-δ expression in infarcted myocardium was highest increased in 3 day after MI and then disappeared in 14 day after MI. GW610742 increased myofibroblast differentiation and transforming growth factor-beta 2 expression in the infarct zone at 7 days after MI. GW610742 also increased bone marrow-derived mesenchymal stem cell (MSC) recruitment in whole myocardium, and increased serum platelet-derived growth factor B, stromal-derived factor-1 alpha, and matrix metallopeptidase 9 levels at day 3 after MI. PPAR-δ agonists treatment have the temporal effect on early fibrosis of infarcted myocardium, which might not sustain the functional and structural beneficial effect.

Influence of platelet reactivity on BARC classification in East Asian patients undergoing percutaneous coronary intervention. Results of the ACCEL-BLEED study.

An increasing body of data suggests that East Asian patients have differing risk profiles for both thrombophilia and bleeding compared with Western population. This study was designed to evaluate the relationship of bleeding to platelet function in East Asians undergoing percutaneous coronary intervention (PCI). Patients who had undergone uneventful PCI (n= 301) were prospectively enrolled and bleeding events were evaluated during dual antiplatelet therapy (DAPT) with aspirin and clopidogrel. Platelet function was measured during hospitalisation and at 30-day follow-up by light transmittance aggregometry (LTA) and vasodilator-stimulated phosphoprotein phosphorylation (VASP-P) assay. During 30-day follow-up, 29.2 % of patients (n= 88) experienced post-discharge Bleeding Academic Research Consortium (BARC) complications (24.6 % and 7.0 % of BARC type 1 and 2, respectively). Patients presenting with acute myocardial infarction had fewer episodes of type 1 BARC bleeding (odds ratio: 0.41; 95 % confidence interval: 0.22 to 0.76; p= 0.005). The cut-off of low platelet reactivity (LPR) (20 µM ADP-induced platelet aggregation ≤ 46.1 %; platelet reactivity index ≤ 45.1 %) was the independent determinant of type 2 BARC bleeding (odds ratio: 3.55 and 4.44; p= 0.009 and 0.002, respectively). The first 30-day BARC bleeding episodes were associated with an increased rate of subsequent premature DAPT discontinuation during one-year follow-up (4.7 % vs 11.4 %; odds ratio: 2.60; 95 % confidence interval: 1.04 to 6.50; p= 0.035). In conclusion, among East Asians, mild bleeding episodes are common early after PCI and are associated with premature DAPT discontinuation. Type 2 BARC bleeding episodes are associated with LPR cut-offs measured at 30 days post-discharge.

Multiple cardiovascular manifestations in a patient with autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) is a systemic disorder associated with various extrarenal complications. The major cardiovascular complications of ADPKD include valvulopathies and vascular ectasia. A 64-year-old man who was diagnosed with ADPKD seven years previously was admitted to our hospital for heart failure. Pelvic computed tomography revealed multiple variable-sized cysts in both kidneys. Transthoracic echocardiography showed enlargement of the left ventricle and left atrium. Severe mitral regurgitation and moderate aortic regurgitation with annuloaortic ectasia were observed. The left main coronary artery was dilated. The patient had various cardiovascular features associated with ADPKD.

Risk stratification using computed tomography coronary angiography in patients undergoing intermediate-risk noncardiac surgery.

OBJECTIVES: This study evaluated whether coronary artery calcium scores (CACS) and the degree of stenosis that were measured with computed tomography coronary angiography (CTCA) predicted post-operative cardiovascular events in patients who were undergoing intermediate-risk noncardiac surgery. BACKGROUND: Cardiovascular complications are important causes of mortality and morbidity in patients undergoing major noncardiac surgeries. METHODS: A total of 239 patients underwent CTCA before intermediate-risk noncardiac surgeries. We measured CACS and the degree of stenosis with CTCA and assessed clinical risk factors according to the revised cardiac risk index (RCRI) scores. Post-operative cardiovascular events were defined as cardiac death, acute coronary syndrome, pulmonary edema, ventricular arrhythmia with hemodynamic compromise, and complete heart block. RESULTS: Nineteen patients (8%) had post-operative cardiac events. The variables that correlated with the occurrence of cardiac events were RCRI (p < 0.001), CACS (p < 0.001), the presence of significant coronary artery stenosis (diameter stenosis ≥50%) (p = 0.01), and multivessel coronary artery disease (p < 0.001). In the receiver-operating characteristic (ROC) curve analysis of CACS for prediction of cardiac events, the cutoff value was 113 (sensitivity, 0.79; specificity, 0.61; area under the curve, 0.762). When comparing ROC curves of the combination models of RCRI, high CACS (≥113), and the presence of multivessel disease, RCRI plus high CACS, RCRI plus multivessel disease, and RCRI plus high CACS plus multivessel disease were significantly more predictable of post-operative cardiovascular events than RCRI alone. CONCLUSIONS: In the pre-operative risk stratification of patients who were undergoing intermediate-risk noncardiac surgeries, CTCA evaluations showed additive value to RCRI.

Accelerated platelet inhibition by switching from atorvastatin to a non-CYP3A4-metabolized statin in patients with high platelet reactivity (ACCEL-STATIN) study.

AIMS: CYP3A4-metabolized statins can influence the pharmacodynamic effect of clopidogrel. We sought to assess the impact of switching to a non-CYP3A4-metabolized statin on platelet function among patients receiving clopidogrel and atorvastatin with high on-treatment platelet reactivity (HPR). METHODS AND RESULTS: Percutaneous coronary intervention (PCI)-treated patients (n= 50) with HPR [20 µM adenosine diphosphate (ADP)-induced maximal platelet aggregation (MPA) >50%] were enrolled during chronic administration of atorvastatin (10 mg/day) and clopidogrel (75 mg/day) (≥6 months). They were randomly assigned to a 15-day therapy with either rosuvastatin 10 mg/day (n= 25) or pravastatin 20 mg/day (n= 25). Platelet function was assessed before and after switching by conventional aggregometry and the VerifyNow P2Y12 assay. Genotyping was performed for CYP2C19*2/*3, CYP3A5*3, and ABCB1 C3435T alleles. The primary endpoint was the absolute change in 20 µM ADP-induced MPA. After switching, MPAs after stimuli with 20 and 5 µM ADP were decreased by 6.6% (95% confidence interval: 3.2-10.1%; P < 0.001), and 6.3% (95% confidence interval: 2.5-10.2%; P = 0.002), respectively. Fifty-two P2Y12 reaction units fell (95% confidence interval: 35-70; P < 0.001) and the prevalence of HPR decreased (24%; P < 0.001). Pharmacodynamic effects were similar after rosuvastatin and pravastatin therapy. In addition to smoking status, the combination of calcium channel blocker usage and ABCB1 C3435T genotype significantly affected the change of 20 µM ADP-induced MPA. CONCLUSIONS: Among PCI-treated patients with HPR during co-administration of clopidogrel and atorvastatin, switching to a non-CYP3A4-metabolized statin can significantly decrease platelet reactivity and the prevalence of HPR. This switching effect appears similar irrespective of the type of non-CYP3A4-metabolized statin.

Isolated mediastinal myeloid sarcoma successfully treated with chemoradiotherapy followed by unrelated allogeneic stem cell transplantation.

A 22-year-old man was diagnosed with isolated mediastinal myeloid sarcoma which radiologically mimicked primary mediastinal lymphoma. Despite administration of standard remission induction chemotherapy with daunorubicin and cytarabine, and three cycles of intensive high-dose cytarabine-based consolidation, chemo-resistant hypermetabolic lesions were persistently detected in the highest mediastinum and in the supraclavicular area. However, complete remission and long-term survival were achieved by curative radiotherapy followed by unrelated allogeneic stem cell transplantation.

Coexistence of chronic myeloid leukemia and pulmonary plasmacytoma mimicking primary lung cancer.

A 61-year-old man was diagnosed with the simultaneous occurrence of chronic myeloid leukemia (CML) and infiltrative intrathoracic plasmacytoma, radiologically mimicking bronchogenic carcinoma. Following the administration of imatinib mesylate (IM; 400 mg/day), both hematologic and partial cytogenetic remission of CML were achieved. However, the pulmonary plasmacytoma was persistently aggravated. High-dose dexamethasone was added to the IM therapy because the patient refused radiotherapy to control the aggravated pulmonary plasmacytoma. Finally, he died due to pneumonia and multi-organ failure during concurrent administration of IM and high-dose dexamethasone.