Association of Intima-Media Thickness Measured at the Common Carotid Artery With Incident Carotid Plaque: Individual Participant Data Meta-Analysis of 20 Prospective Studies.

Background The association between common carotid artery intima-media thickness (CCA-IMT) and incident carotid plaque has not been characterized fully. We therefore aimed to precisely quantify the relationship between CCA-IMT and carotid plaque development. Methods and Results We undertook an individual participant data meta-analysis of 20 prospective studies from the Proof-ATHERO (Prospective Studies of Atherosclerosis) consortium that recorded baseline CCA-IMT and incident carotid plaque involving 21 494 individuals without a history of cardiovascular disease and without preexisting carotid plaque at baseline. Mean baseline age was 56 years (SD, 9 years), 55% were women, and mean baseline CCA-IMT was 0.71 mm (SD, 0.17 mm). Over a median follow-up of 5.9 years (5th-95th percentile, 1.9-19.0 years), 8278 individuals developed first-ever carotid plaque. We combined study-specific odds ratios (ORs) for incident carotid plaque using random-effects meta-analysis. Baseline CCA-IMT was approximately log-linearly associated with the odds of developing carotid plaque. The age-, sex-, and trial arm-adjusted OR for carotid plaque per SD higher baseline CCA-IMT was 1.40 (95% CI, 1.31-1.50; I2=63.9%). The corresponding OR that was further adjusted for ethnicity, smoking, diabetes, body mass index, systolic blood pressure, low- and high-density lipoprotein cholesterol, and lipid-lowering and antihypertensive medication was 1.34 (95% CI, 1.24-1.45; I2=59.4%; 14 studies; 16 297 participants; 6381 incident plaques). We observed no significant effect modification across clinically relevant subgroups. Sensitivity analysis restricted to studies defining plaque as focal thickening yielded a comparable OR (1.38 [95% CI, 1.29-1.47]; I2=57.1%; 14 studies; 17 352 participants; 6991 incident plaques). Conclusions Our large-scale individual participant data meta-analysis demonstrated that CCA-IMT is associated with the long-term risk of developing first-ever carotid plaque, independent of traditional cardiovascular risk factors.

Prasugrel-Based De-Escalation in Patients With Acute Coronary Syndrome According to Renal Function.

Background: Patients with coronary artery disease and impaired renal function are at higher risk for both bleeding and ischemic adverse events after percutaneous coronary intervention (PCI). Objectives: This study assessed the efficacy and safety of a prasugrel-based de-escalation strategy in patients with impaired renal function. Methods: We conducted a post hoc analysis of the HOST-REDUCE-POLYTECH-ACS study. Patients with available estimated glomerular filtration rate (eGFR) (n = 2,311) were categorized into 3 groups. (high eGFR: >90 mL/min; intermediate eGFR: 60 to 90 mL/min; and low eGFR: <60 mL/min). The end points were bleeding outcomes (Bleeding Academic Research Consortium type 2 or higher), ischemic outcomes (cardiovascular death, myocardial infarction, stent thrombosis, repeated revascularization, and ischemic stroke), and net adverse clinical event (including any clinical event) at 1-year follow-up. Results: Prasugrel de-escalation was beneficial regardless of baseline renal function (P for interaction = 0.508). The relative reduction in bleeding risk from prasugrel de-escalation was higher in the low eGFR group than in both the intermediate and high eGFR groups (relative reductions, respectively: 64% (HR: 0.36; 95% CI: 0.15-0.83) vs 50% (HR: 0.50; 95% CI: 0.28-0.90) and 52% (HR: 0.48; 95% CI: 0.21-1.13) (P for interaction = 0.646). Ischemic risk from prasgurel de-escalation was not significant in all eGFR groups (HR: 1.18 [95% CI: 0.47-2.98], HR: 0.95 [95% CI: 0.53-1.69], and HR: 0.61 [95% CI: 0.26-1.39]) (P for interaction = 0.119). Conclusions: In patients with acute coronary syndrome receiving PCI, prasugrel dose de-escalation was beneficial regardless of the baseline renal function.

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.

Anderson-Fabry disease presenting with atrial fibrillation as earlier sign in a young patient: A case report.

BACKGROUND: Anderson-Fabry disease (AFD) is an X-linked lysosomal storage disorder that results from a deficiency of α-galactosidase A enzyme activity in which glycosphingolipids gradually accumulate in multi-organ systems. Cardiac manifestations are the leading cause of mortality in patients with AFD. Among them, arrhythmias comprise a large portion of the heart disease cases in AFD, most of which are characterized by conduction disorders. However, atrial fibrillation as a presenting sign at the young age group diagnosed with AFD is uncommon. CASE SUMMARY: We report a case of a 26-year-old man who was admitted with chest discomfort. Left ventricular hypertrophy was fulfilled in the criteria by the Sokolow-Lyon index and atrial fibrillation on the 12 Leads-electrocardiography (ECG) that was documented in the emergency room. After spontaneously restored to normal sinus rhythm, relationships between P and R waves, including a shorter PR interval on the ECG, were revealed. The echocardiographic findings showed thickened interventricular septal and left posterior ventricular walls. Based on the clues mentioned earlier, we realized the possibility of AFD. Additionally, we noticed the associated symptoms and signs, including bilateral mild hearing loss, neuropathic pain, anhidrosis, and angiokeratoma on the trunk and hands. He was finally diagnosed with classical AFD, which was confirmed by the gene mutation and abnormal enzyme activity of α-galactosidase A. CONCLUSION: This case is a rare case of AFD as a presentation with atrial fibrillation at a young age. Confirming the relationship between P and Q waves on the ECG through sinus rhythm conversion may help in differential diagnosis of the cause of atrial fibrillation and hypertrophic myocardium.

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).

Erratum to cardiac arrest due to coronary embolism from a metastatic sarcoma recovered through aspiration thrombectomy.

[This corrects the article DOI: 10.21037/jtd.2018.05.133.].

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.

Treatment of Adenoviral Acute Respiratory Distress Syndrome Using Cidofovir With Extracorporeal Membrane Oxygenation.

Adenovirus infections are associated with respiratory (especially upper respiratory) infection and gastrointestinal disease and occur primarily in infants and children. Although rare in adults, severe lower respiratory adenovirus infections including pneumonia are reported in specific populations, such as military recruits and immunocompromised patients. Antiviral treatment is challenging due to limited clinical experience and lack of well-controlled randomized trials. Several previously reported cases of adenoviral pneumonia showed promising efficacy of cidofovir. However, few reports discussed the efficacy of cidofovir in acute respiratory distress syndrome (ARDS). We experienced 3 cases of adenoviral pneumonia associated with ARDS and treated with cidofovir and respiratory support, including extracorporeal membrane oxygenation (ECMO). All 3 patients showed a positive clinical response to cidofovir and survival at 28 days. Cidofovir with early ECMO therapy may be a therapeutic option in adenoviral ARDS. A literature review identified 15 cases of adenovirus pneumonia associated with ARDS.

Early- and late-term clinical outcome and their predictors in patients with ST-segment elevation myocardial infarction and non-ST-segment elevation myocardial infarction.

BACKGROUNDS: The disparity between ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) remains controversial. We compared clinical outcomes and prognostic factors between STEMI and NSTEMI using large-scale registry data. METHODS: We recruited 28,421 patients with STEMI (n=16,607) and NSTEMI (n=11,814) between November 2005 and April 2010 from a nationwide registry in Korea. We performed landmark analysis of cardiac death, recurrent acute myocardial infarction (re-AMI), revascularization, and major adverse cardiac events (MACE) at 30 days (early term) and 1 year (late term) after admission. RESULTS: Patients with NSTEMI had a greater number of co-morbidities than STEMI patients. Early term MACE (6.9% vs. 4.5%, p<0.001) and cardiac death (6.1% vs. 3.7%, p<0.001) were higher in STEMI patients. However, late-term MACE (8.0% vs. 9.1%, p=0.007), cardiac death (1.9% vs. 2.6%, p=0.001), and re-AMI (0.6% vs. 1.3%, p<0.001) were lower in the STEMI group. The independent predictors of cardiac death were old age, renal dysfunction, LV dysfunction, Killip class, post-thrombolysis in myocardial infarction (TIMI) flow, and major bleeding in both groups. Female gender, previous ischemic heart disease, diabetes, current smoking, multivessel disease, and body mass index were MI type- or time-dependent predictors. CONCLUSION: The STEMI group displayed poor early term clinical outcome, whereas the NSTEMI group displayed poor late-term clinical outcome. The STEMI and NSTEMI groups had different predictor profiles for cardiac death, suggesting that different strategies are required for improving the late-term outcome of STEMI and NSTEMI patients.

Hypercholesterolemia and in-vivo coronary plaque composition in patients with coronary artery disease: a virtual histology - intravascular ultrasound study.

BACKGROUND AND OBJECTIVES: Hypercholesterolemia is a key factor in the development of atherosclerosis. We sought to evaluate the relation between hypercholesterolemia and plaque composition in patients with coronary artery disease. SUBJECTS AND METHODS: Study subjects consisted of 323 patients (mean 61.5 years, 226 males) who underwent coronary angiography and virtual histology-intravascular ultrasound examination. Patients were divided into two groups according to total cholesterol level: hypercholesterolemic group (≥200 mg/dL, n=114) and normocholesterolemic group (<200 mg/dL, n=209). RESULTS: Hypercholesterolemic patients were younger (59.7±13.3 years vs. 62.6±11.5 years, p=0.036), than normocholesterolemic patients, whereas there were no significant differences in other demographics. Hypercholesterolemic patients had higher corrected necrotic core volume (1.23±0.85 mm(3)/mm vs. 1.02±0.80 mm(3)/mm, p=0.029) as well as percent necrotic core volume (20.5±8.5% vs. 18.0±9.2%, p=0.016) than normocholesterolemic patients. At the minimal lumen area site, percent necrotic core area (21.4±10.5% vs. 18.4±11.3%, p=0.019) and necrotic core area (1.63±1.09 mm(2) vs. 1.40±1.20 mm(2), p=0.088) were also higher than normocholesterolemic patients. Multivariate linear regression analysis showed that total cholesterol level was an independent factor of percent necrotic core volume in the culprit lesion after being adjusted with age, high density lipoprotein-cholesterol , hypertension, diabetes mellitus, smoking and acute coronary syndrome (beta 0.027, 95% confidence interval 0.02-0.053, p=0.037). CONCLUSION: Hypercholesterolemia was associated with increased necrotic core volume in coronary artery plaque. This study suggests that hypercholesterolemia plays a role in making plaque more complex, which is characterized by a large necrotic core, in coronary artery disease.

Tailored surgical approaches for benign craniovertebral junction tumors.

OBJECTIVE: We report our surgical experience in the treatment of 16 consecutive patients with benign craniovertebral junction (CVJ) tumor, observed from 2003 to 2008 at our department. METHODS: We had treated 6 foramen magnum meningiomas, 6 cervicomedullary hemangioblastomas, 1 accessory nerve schwannoma, 1 hypoglossal nerve schwannoma, 1 C2 root schwannoma, and 1 cavernous hemangioma. Clinical results were evaluated by Karnofsky Performance Scale (KPS) and all patients underwent preoperative neuroradiological evaluation with computed tomography (CT) and magnetic resonance image (MRI). Angiography was performed in 15 patients and preoperative embolization was done in 2 patients. RESULTS: Five far-lateral, 1 supracondylar and 10 midline suboccipital approaches were performed. Gross total removal was achieved in 15 cases (94%) and subtotal removal in 1 patient (6%). None of the patients required occipitocervical fusion. Radiological follow-up showed no recurrence in cases totally removed. Postoperative decrease of KPS scores was recorded in only 1 patient. The treatment of cervicomedullary solid hemangioblastoma presented particular issues : by preoperative embolization, we removed tumor totally without an excessive bleeding or brainstem injury. In one of foramen magnum meningioma, we carried out subtotal removal due to hard tumor consistency and encasement of neurovascular structures. CONCLUSION: : The choice of surgical approaches and the extent of bone resection should be defined according to the location and size of individual tumors. Moreover, we emphasize that preoperative neuroradiological evaluations on presumptive tumor type could be helpful to the surgeon in tailoring the technique and providing the required exposure for different lesions, without unnecessary surgical steps.

Low contribution of BRCA1/2 genomic rearrangement to high-risk breast cancer in the Korean population.

Genomic rearrangement occasionally affects the BRCA1/2 genes in Caucasian breast cancer patients. However, the incidence of BRCA1/2 genomic rearrangement in Asians, including the Korean population, has not been well established. Here, we investigated the contribution of BRCA1/2 genomic rearrangement to high-risk breast cancer patients in this population. We screened for BRCA1/2 genomic rearrangement using multiplex ligation-dependent probe amplification for 122 high-risk breast cancer patients who tested negative for BRCA1/2 mutations. A novel deletion of exons 13-15 in BRCA1 was identified in one patient (0.8% occurrence frequency). Further analyses revealed that this c.4186-1593_4676-1465del might be the result of homologous recombination mediated by two Alu-elements: the AluY in intron 12, and an AluSp in intron 15. This result suggests that subsequent screening for BRCA1/2 genomic rearrangements should be considered in high-risk Korean breast cancer patients who test negative for BRCA1/2 mutations. BRCA1/2 genomic rearrangement, however, is likely to make only a small contribution to breast cancer in this population.

Intra-suprasellar schwannoma originating from the diaphragma sellae.

A 49-year-old woman presented with headache, vomiting and visual disturbance. Neurological examination revealed bitemporal hemianopsia with poor visual acuity. Magnetic resonance imaging showed a bulky intra-suprasellar mass, which was isointense with brain parenchyma on T1-weighted images, and slightly hyperintense on T2-weighted images. After gadolinium administration, the mass was homogeneously enhanced. The mass was partially removed by the endonasal transsphenoidal approach and then the remnant mass was totally removed by the transcranial approach five months later. We found a yellowish mass which was attached to the diaphragm sellae in operation field. Histopathological examination of the tumor revealed the characteristic features of a schwannoma. We report an unusual case of an intra-suprasellar schwannoma resembling a non-functioning pituitary macroadenoma both clinically and radiologically.