Irreversible evolutionary loss of chitin-degrading ability in the chitinase-like protein Ym1 under positive selection in rodents.

Ym1 (chitinase-like 3, Chil3) expressed in mice is a nonenzymatic chitinase-like protein, which shows 67% identity with mouse acidic chitinase (Chia). Similar to Chia, Ym1 is overexpressed in asthma and parasitic infections in mouse lungs. Due to the lack of chitin-degrading activity, the biomedical role of Ym1 under these pathophysiological conditions remains to be determined. In this study, we investigated what region and amino acid changes in Ym1 resulted in the loss of enzymatic activity. Replacing two amino acids at the catalytic motif to obtain a Chia-like sequence (N136D and Q140E; MT-Ym1) did not activate the protein. We conducted a comparative study of Ym1 and Chia. We found that three protein segments-(i) the catalytic motif residues, (ii) exons 6 and 7, and (iii) exon 10-are responsible for chitinase activity loss in Ym1. We show that replacing each of these three segments in Chia that are also involved in substrate recognition and binding by the Ym1 sequence can fully abolish the enzymatic activity. In addition, we show that there have been extensive gene duplication events at the Ym1 locus specific to the rodent lineages. Consistent with this result, Ym1 orthologs from the rodent genome were under positive selection when analyzed through the CODEML program. These data suggest that numerous amino acid substitutions in the regions involved in the chitin recognition, binding, and degradation ability of the ancestor Ym1 molecule lead to the irreversible inactivation of the protein.

Femoral Vein Occlusion or Stenosis Using a Suture-Mediated Vascular Closure Device After Catheter Ablation.

A suture-mediated vascular closure device is useful for hemostasis of the femoral vein after catheter ablation; however, venous complications remain unclear. We encountered 2 cases of femoral vein occlusion and stenosis using a suture-mediated vascular closure device. Both patients underwent surgical repair and recovered venous flow. (Level of Difficulty: Intermediate.).

Prognostic impact of hospital-acquired disability in elderly patients with heart failure.

AIMS: Functional decline is associated with worse outcomes in patients with elderly heart failure (HF), but little is known about the prognostic impact of hospital-acquired disability (HAD) during hospital stay after acute HF. The present study examines the prognostic significance of HAD in the prediction of all-cause mortality in elderly patients who admitted for acute HF. METHODS AND RESULTS: This retrospective study was performed in 1941 elderly patients aged ≥65 years or older from the cardiovascular physiotherapy for acute HF patients in the Tokyo metropolitan area registry and excluded those who died in hospital. HAD was defined as any decline in the Barthel index (BI) before discharge compared with the BI within 1 month before hospital admission. The primary outcome of this study was all-cause death and HF readmission. A total of 565 (29%) deaths and 789 (41%) HF readmission occurred over a median follow-up period of 1.7 years. A total of 476 patients (25%) had HAD during hospital stay after acute HF. In multivariable analysis, HAD predicted all-cause death [hazard ratio (HR): 1.772; 95% confidence interval (CI): 1.450-2.167; P < 60; 0.001] and with risk of HF readmission (HR: 1.193; 95% CI: 1.005-1.416; P = 0.043) after adjusting for the Meta-analysis Global Group in Chronic Heart Failure risk score. CONCLUSIONS: Hospital-acquired disability is associated with an increased risk of all-cause death and readmission for HF in elderly patients with acute HF.

Predictors of the "Crosstalk" Phenomenon During Cryoballoon Ablation in Patients with Atrial Fibrillation.

Second-generation cryoballoon (CB) ablation is effective in achieving pulmonary vein (PV) isolation (PVI) in atrial fibrillation (AF) patients. The "crosstalk" (CST) phenomenon has been reported to reduce unnecessary applications during CB ablation. Nevertheless, it is unclear under what conditions the CST phenomenon occurs.To seek the predictors of the CST phenomenon during CB-guided PVI, CST phenomenon in achieving ipsilateral superior PVI during inferior PV ablation was analyzed in AF patients who underwent de novo ablation using CB. CB occlusion status and nadir balloon temperature (NT) were compared in these patients, and all ablated superior PVs were categorized into three groups according to the necessity of the touch up ablation and effectiveness of the phenomenon.Of 1082 superior PVs, 16, 40, and 1026 were classified into the CST success, CST failure, and control groups (unnecessary CST), respectively. The proportion of superior PVs ablated with complete occlusion using the CB was significantly higher in the CST success group than in the other two groups. The proportion of superior PVs ablated with NT ≤ -46°C was higher in the CST success group than in the CST failure group. The CST phenomenon was always observed if CB ablation of the superior PVs was performed with both complete occlusion and NT ≤ -46°C and was almost always ineffective if it did not meet these two criteria (sensitivity, 100%; specificity, 93%).Successful CST ablation was highly predicted if complete PV occlusion and NT ≤ -46°C during CB ablation of the superior PVs were achieved.

The clinical impact of the left atrial posterior wall lesion formation by the cryoballoon application for persistent atrial fibrillation: Feasibility and clinical implications.

INTRODUCTION: The left atrial (LA) posterior wall (LAPW) has been targeted to improve the clinical outcomes in patients with persistent atrial fibrillation (PersAF). This study aimed to investigate the feasibility, safety, and clinical implications of cryoballoon (CB) applications on the LAPW to accomplish electrical isolation (EI) of the LAPW with CB. METHODS: A total of 100 patients (males, 84; mean age, 64 ± 10 years) with PersAF were enrolled. The first 50 patients underwent only pulmonary vein isolation (PVI) (PVI-only group) and the remaining 50 patients underwent PVI and EI of the LAPW with CB (EI-LAPW group). RESULTS: One-year sinus rhythm maintenance probability was significantly higher in the EI-LAPW group than in PVI-only group (80.0% vs 55.1%, P = 0.01). The success rate of constructing an LA roof block line (LA-RB), bottom block line, and EI of the LAPW was 92%, 60%, and 58%, respectively. The nadir CB temperature (-45°C ± 4°C vs -39°C ± 5°C, P = 0.005) and anatomical angle of the left atrial roof (106°C ± 30°C vs 144°C ± 17°C, P < 0.001) significantly predicted the successful LA-RB construction. The left ventricular ejection fraction was significantly higher in unsuccessful cases than in successful cases of an EI of the LAPW (64% ± 8% vs 58% ± 11%, P = 0.041). Even though the EI of the LAPW was unsuccessful, CB freezing in LAPW significantly debulked the nonscar area (≥0.1 mV) in LAPW (18.1 ± 5.6 vs 2.2 ± 3.1 cm 2 , P < 0.001) and provided the equivalent 1-year outcome of successful cases (79.3% vs 81.0%, P = 0.90). CONCLUSION: The combination of PVI and EI of the LAPW with CB provided better clinical outcomes than conventional PVI procedure for patients with PersAF.

Clinical investigation of esophageal injury from cryoballoon ablation of persistent atrial fibrillation.

BACKGROUND: The cryoballoon (CB) can be utilized for extra pulmonary vein (PV) ablation such as for a left atrial (LA) posterior wall (LAPW) isolation. However, scrutiny of the esophageal injuries during the LAPW isolation has never been performed. We sought to thoroughly investigate the esophageal lesions (ELs) and gastric hypomotility (GH) caused by an LAPW isolation using a CB. METHODS: A total of 101 persistent atrial fibrillation patients who underwent an LAPW isolation using a CB were enrolled. The CB was applied on the roof and bottom area of the LAPW after a PV isolation. The luminal esophageal temperature (LET) was monitored by a thermistor probe during the CB applications. When the LET reached 15°C, the freezing application was prematurely interrupted. Esophagogastroscopy was performed on the next day following the ablation. RESULTS: All PVs were successfully isolated in all patients. A successful LAPW isolation solely with CB ablation was performed in 72 (71.3%) patients. Cryofreezing applications were prematurely interrupted due to low LETs in 49 (48.5%) patients predominantly during the LA bottom line ablation. ELs and GH were observed in 11 (10.9%) and 16 patients (15.8%), respectively. The nadir LET tended to be lower in patients with ELs and GH than in those without (ELs: 14.8 ± 4.5°C vs 17.4 ± 6.0°C, P = 0.17; GH: 15.5 ± 4.5°C vs 17.5 ± 6.1°C, P = 0.23, respectively). CONCLUSIONS: Esophageal complications such as ELs and GH occur during the LAPW isolation with a CB. There was no reliable predictor of those adverse events.

"Clinical Impact of the Cryoballoon Temperature and Occlusion Status on the Success of Pulmonary Vein Isolation".

BACKGROUND: Complete occlusion of the pulmonary veins (PVs) with the cryoballoon (CB) is considered to be the crucial factor for a successful PV isolation (PVI). We investigated whether a complete occlusion was indispensable for a successful CB based PVI of every PV. METHODS AND RESULTS: Atrial fibrillation patients (n=123, 97; paroxysmal) undergoing a de novo PVI were enrolled. A total of 477 PVs were analyzed. The occlusion grade (OG) was scored as follows: OG3 (complete occlusion), OG2 (incomplete occlusion with slight leakage), OG1 (poor occlusion with massive leakage). There was no significant difference in the CB temperature (CBT) at all measured time points (from 30 to 120sec after freezing) and nadir CBT between OG2 and OG3 in all PVs except for the right inferior PV (RIPV). The RIPV isolation success rate was significantly lower for the OG2 status than OG3 (97.5 vs. 57.6%; p<0.0001). In contrast, there was not significant difference in the isolation success rate of the other three PVs between OG2 and OG3. In particular, the success rate of the right superior PV (RSPV) isolation was >95% for both OG2 and OG3. Phrenic nerve paralysis (PNP) was provoked during the RSPV isolation in two patients in whom the RSPVs were frozen during OG3. CONCLUSION: An OG3 may not always be required for a successful PVI of all PVs except the RIPV. OG2 could have comparable effects as OG3 in terms of a successful RSPV isolation. Not aiming for OG3 for the RSPV may reduce the risk of PNP.

Clinical assessment of cryoballoon ablation in cases with atrial fibrillation and a left common pulmonary vein.

INTRODUCTION: Pulmonary vein isolation (PVI) using a cryoballoon (CB) is a useful tool for treating atrial fibrillation (AF); however, the clinical efficacy of the CB has never been fully investigated in patients with a left common pulmonary vein (LCPV). METHODS AND RESULTS: Three hundred twenty-four consecutive paroxysmal AF patients underwent PVI with a CB. Three-dimensional computed tomography was performed in all patients before the ablation. The clinical outcomes of the AF ablation between patients with (Group A) and without an LCPV (Group B) were compared. An LCPV was observed in 27 (8%) patients. There were no significant differences in the procedure time (149 ± 45 min vs. 143 ± 40 min, respectively; P = 0.42) and percentage needing touch up ablation between the 2 groups (26% vs. 20%, respectively; P = 0.45). At a mean follow-up of 454 ± 195 days, 282 of 324 (87%) patients were free from any atrial tachyarrhythmias (ATs) after a single procedure. Twenty out of 27 (74%) Group A patients and 262 of 297 (88%) Group B patients were free from ATs (15-month Kaplan-Meier event free rate estimates, 77% and 89%, respectively; P = 0.02). A multivariate analysis identified the presence of an LCPV and the left atrial diameter as reliable predictors of recurrent ATs. CONCLUSIONS: The long-term clinical outcomes of ablation of AF with the CB was worse in patients with an LCPV than in those without. The presence of an LCPV and the LA size seemed to be reliable predictors of a worse outcome.

Ultra-long acting calcium channel blockers may decrease accuracy of the acetylcholine provocation test.

BACKGROUND: When drug-induced coronary spasm provocation tests are performed, a washout period of >48h for calcium channel blockers (CCBs) is uniformly recommended. However, each CCB has a distinct half-life, and little is known about the influence of prior oral administration of CCBs on acetylcholine provocation test to evaluate coronary vasomotor reaction. METHODS AND RESULTS: We examined 245 consecutive patients with suspected vasospastic angina who had undergone acetylcholine provocation test. Of those patients, 29 patients had been on amlodipine, an ultra-long term acting CCB (group A), 34 on other CCBs (group O), and 182 patients on no CCB (group N). After CCBs had been withheld > 48h, we performed acetylcholine provocation, which resulted in 152 positive, 36 intermediate, and 57 negative reactions. We evaluated coronary artery tone calculated as follows: (luminal diameter after nitrate-baseline luminal diameter)÷(luminal diameter after nitrate)×100 (%). In group A patients, coronary artery tone was lower (A:9.1±6.9% vs. O:11.7±8.3% vs. N:12.1±8.5%, p=0.0011) and the positive rate of acetylcholine provocation test was lower than group O and group N (A:41% vs. O:68% vs. N:64%, p=0.047). Multivariate logistic analysis showed that taking amlodipine until 2days before acetylcholine provocation test was a significant inverse predictor for acetylcholine-provoked coronary spasm (odds ratio 0.327; 95% confidence interval 0.125-0.858, p=0.023). CONCLUSIONS: Residual vasodilatory effects of ultra-long acting CCB may decrease coronary artery tone and the vasoconstrictive reaction to acetylcholine suggesting that a 2-day pre-test drug holiday may not be long enough.

Comparative study of hemorrhagic and ischemic complications among anticoagulants in patients undergoing cryoballoon ablation for atrial fibrillation.

OBJECTIVE: Few data exist to evaluate the safety and efficacy of direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) undergoing cryoballoon ablation (CB-A). This study is aimed to clarify the usefulness of DOACs in patients undergoing CB-A. METHODS: The patients (average age; 65.8±11.9 years old, male 69%) were stratified into one of five subsets based on the type of anticoagulation (warfarin, apixaban, dabigatran, rivaroxaban, or edoxaban), and underwent CB-A. A brain MRI was performed in all patients the day after the CB-A for AF. A total of 257 (19 on warfarin, 30 on apixaban, 66 on dabigatran, 81 on rivaroxaban, and 61 on edoxaban) patients met the inclusion criteria. RESULTS: The incidence of silent cerebral ischemic lesion was 1 (11.1%) patients on warfarin, 5 (33.3%) on apixaban, 8 (27.6%) on dabigatran, 10 (21.3%) on rivaroxaban, and 10 (29.4%) on edoxaban (p=0.17). Major ischemic events occurred in one patient (1.6%) on edoxaban and one (5.3%) on warfarin. Minor bleeding complications occurred in 1 patient (5.3%) on warfarin, 2 (6.7%) on apixaban, 1 (1.2%) on rivaroxaban, 5 (7.6%) on dabigatran, and 2 (3.3%) on edoxaban (p=0.24). Of note, major bleeding complications occurred in 2 patients (3.3%) on apixaban, 1 (1.2%) on rivaroxaban, 1 (1.5%) on dabigatran, 1 (1.6%) on edoxaban, and 2 (10.5%) on warfarin (p<0.05). CONCLUSIONS: Warfarin use significantly increased the risk of serious bleeding, in contrast, CB-A did not place the patients at an increased risk of complications under a DOAC treatment. There were no significant differences regarding preventing embolic events among the DOAC drugs.

Regulation of Cardiac Transcription Factor GATA4 by Post-Translational Modification in Cardiomyocyte Hypertrophy and Heart Failure.

Heart failure is a leading cause of cardiovascular mortality in industrialized countries. During development and deterioration of heart failure, cardiomyocytes undergo maladaptive hypertrophy, and changes in the cellular phenotype are accompanied by reinduction of the fetal gene program. Gene expression in cardiomyocytes is regulated by various nuclear transcription factors, co-activators, and co-repressors. The zinc finger protein GATA4 is one such transcription factor involved in the regulation of cardiomyocyte hypertrophy. In response to hypertrophic stimuli such as those involving the sympathetic nervous and renin-angiotensin systems, changes in protein interaction and/or post-translational modifications of GATA4 cause hypertrophic gene transcription in cardiomyocytes. In this article, we focus on cardiac nuclear signaling molecules, especially GATA4, that are promising as potential targets for heart failure therapy.

Tyrosine phosphorylation of RACK1 triggers cardiomyocyte hypertrophy by regulating the interaction between p300 and GATA4.

The zinc finger protein GATA4 is a transcription factor involved in cardiomyocyte hypertrophy. It forms a functional complex with the intrinsic histone acetyltransferase (HAT) p300. The HAT activity of p300 is required for the acetylation and transcriptional activity of GATA4, as well as for cardiomyocyte hypertrophy and the development of heart failure. In the present study, we have identified Receptor for Activated Protein Kinase C1 (RACK1) as a novel GATA4-binding protein using tandem affinity purification and mass spectrometry analyses. We found that exogenous RACK1 repressed phenylephrine (PE)-induced hypertrophic responses, such as myofibrillar organization, increased cell size, and hypertrophy-associated gene transcription, in cultured cardiomyocytes. RACK1 physically interacted with GATA4 and the overexpression of RACK1 reduced PE-induced formation of the p300/GATA4 complex and the acetylation and DNA binding activity of GATA4. In response to hypertrophic stimulation in cultured cardiomyocytes and in the hearts of hypertensive heart disease model rats, the tyrosine phosphorylation of RACK1 was increased, and the binding between GATA4 and RACK1 was reduced. In addition, the tyrosine phosphorylation of RACK1 was required for the disruption of the RACK1/GATA4 complex and for the formation of the p300/GATA4 complex. These findings demonstrate that RACK1 is involved in p300/GATA4-dependent hypertrophic responses in cardiomyocytes and is a promising therapeutic target for heart failure.

Novel method for earlier detection of phrenic nerve injury during cryoballoon applications for electrical isolation of pulmonary veins in patients with atrial fibrillation.

BACKGROUND: Diaphragmatic electrogram recording during cryoballoon ablation (CB-A) of atrial fibrillation is commonly used to predict phrenic nerve palsy (PNP). OBJECTIVE: The purpose of this study was to investigate a novel method for predicting PNP at an earlier stage to prevent sustained PNP. METHODS: A total of 197 patients undergoing CB-A were enrolled. We attempted to detect PNP using fluoroscopic images of diaphragmatic contractions and by monitoring diaphragmatic compound motor action potentials (CMAPs) provoked by superior vena cava (SVC) and left subclavian vein (LCV) pacing during CB-A for bilateral pulmonary veins (PVs). Pacing of the SVC and LCV was performed at 2 outputs, 1 exceeding the pacing threshold by 10% (MIN) and the other at maximum output (MAX). The time from freezing to the initiation of PNP, values of the CMAP amplitude, and severity of PNP were compared for the 2 outputs. RESULTS: There was a significant difference in the time from freezing to initiation of PNP between MIN and MAX pacing (25.7 ± 5.7 vs 81.3 ± 7.4 seconds, P<.01). CMAP amplitudes also differed significantly (0.71 ± 0.39 vs 1.13 ± 0.42, P<.0001). SVC/LCV pacing with MIN output was able to detect PNP significantly earlier than MAX (27 ± 8 vs 91 ± 12 seconds, P<.01), and the time to PNP recovery was significantly shorter for the MIN output (20.2 ± 8.88 hours vs 4.8 ± 1.6 months, P<.001). CONCLUSION: Pacing the SVC and LCV with lower output detect PNP significantly earlier than maximal output pacing and leads to recovery from PNP on the order of hours postprocedure rather than months.

Ventricular Fibrillation in a Patient with Multi-Vessel Coronary Spasm Four Days after the Initiation of an Oral Beta-blocker.

We describe a case of ventricular fibrillation occurring in a patient with multi-vessel coronary spasm after the initiation of an oral beta-blocker. A 56-year-old man began to experience chest discomfort and his computed tomography revealed intermediate coronary stenoses. He was administered medications including an oral beta-blocker but suddenly collapsed while walking 4 days later. An automated external defibrillator detected ventricular fibrillation and delivered successful electrical cardioversion. An acetylcholine provocation test after stabilization of the status revealed triple-vessel coronary spasm. Beta-blockers may provoke exacerbation of coronary spasm and result in lethal arrhythmia. LEARNING POINTS: Beta-blockers which have a vasoconstrictive effect may occasionally provoke exacerbation of coronary spasm.Coronary spasm should be considered as a cause of lethal ventricular arrhythmia or cardiac arrest.

Effects of Statins on Left Ventricular Diastolic Function in Patients with Dyslipidemia and Diastolic Dysfunction (Stat-LVDF Study).

Statins, 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors, are potential drugs for chronic heart failure treatment in clinical studies. However, there may be differences in the effects on heart failure between lipophilic and hydrophilic statins. In this study, we investigated whether hydrophilic rosuvastatin (RSV) and lipophilic pitavastatin (PTV) exert different effects on the left ventricular diastolic function. Subjects were hypercholesterolemia patients with left ventricular diastolic dysfunction. This was an open-label, randomized, parallel, comparative, prospective study. The subjects received treatment with RSV or PTV for 24 weeks, and their low density lipoprotein (LDL)-cholesterol levels were controlled by these statins according to the guideline. The primary endpoint was defined as the change in left ventricle (LV) diastolic function (E/E') estimated by echocardiography, and the secondary endpoint was the plasma B-type natriuretic peptide (BNP) level. No serious adverse effects were observed during the entire study period in any patient, nor were there any significant differences in changes in the body mass index, blood pressure, or heart rate. Statin treatment did not significantly alter the primary endpoint, E/E'. The change ratio of BNP was not significantly different between PTV and RSV groups. However, BNP was significantly increased in the RSV (p=0.030) but not the PTV (p>0.999) group. This study revealed that although neither RSV nor PTV improved LV diastolic dysfunction, BNP, a biomarker of LV wall stress, was increased in the RSV but not the PTV group. Observation for a longer period is necessary to clarify the different effects of these statins on LV diastolic dysfunction. (UMIN-ID: UMIN000003571).

Colloidal submicron-particle curcumin exhibits high absorption efficiency-a double-blind, 3-way crossover study.

Curcumin is a major constituent of the spice turmeric and has various biological activities, including anticancer, antioxidant, and anti-inflammatory properties, as well as alcohol detoxification. However, because of its poor absorption efficiency, it is difficult for orally administered curcumin to reach blood levels sufficient to exert its bioactivities. To overcome this problem, several curcumin preparations with a drug-delivery system (DDS) have been developed to increase the bioavailability of curcumin after oral administration, and tested as functional foods and potential medical agents in humans. We have also produced capsules containing Theracurmin, curcumin dispersed with colloidal submicron-particles. To evaluate the absorption efficiency of three types of DDS curcumin, we performed a double-blind, 3-way crossover study. We compared plasma curcumin levels after the administration of Theracurmin and 2 other capsule types of curcumin with DDS, BCM-95 (micronized curcumin with turmeric essential oils) and Meriva (curcumin-phospholipid). Nine healthy subjects (male/female=5/4, age: 24-32 y old) were administered these 3 preparations of DDS curcumin, at commonly used dosages. Six capsules of Theracurmin, 1 capsule of BCM-95, and 2 capsules of Meriva contain 182.4 ± 1.0, 279.3 ± 10.7, and 152.5 ± 20.3 mg of curcumin, respectively. The maximal plasma curcumin concentration (0-24 h) of Theracurmin was 10.7 to 5.6 times higher than those of BCM-95 and Meriva, respectively. Moreover, the area under the blood concentration-time curve at 0-24 h was found to be 11.0- and 4.6-fold higher with Theracurmin than BCM-95 and Meriva, respectively. These data indicate that Theracurmin exhibits a much higher absorption efficiency than other curcumin DDS preparations.

Optimal dose-setting study of curcumin for improvement of left ventricular systolic function after myocardial infarction in rats.

A natural p300-specific histone acetyltransferase inhibitor, curcumin, may have a therapeutic potential for heart failure. However, a study of curcumin to identify an appropriate dose for heart failure has yet to be performed. Rats were subjected to a left coronary artery ligation. One week later, rats with a moderate severity of myocardial infarction (MI) were randomly assigned to 4 groups receiving the following: a solvent as a control, a low dose of curcumin (0.5 mg∙kg(-1)∙day(-1)), a medium dose of curcumin (5 mg∙kg(-1)∙day(-1)), or a high dose of curcumin (50 mg∙kg(-1)∙day(-1)). Daily oral treatment was continued for 6 weeks. After treatment, left ventricular (LV) fractional shortening was dose-dependently improved in the high-dose (25.2% ± 1.6%, P < 0.001 vs. vehicle) and medium-dose (19.6% ± 2.4%) groups, but not in the low-dose group (15.5% ± 1.4%) compared with the vehicle group (15.1% ± 0.8%). The histological cardiomyocyte diameter and perivascular fibrosis as well as echocardiographic LV posterior wall thickness dose-dependently decreased in the groups receiving high and medium doses. The beneficial effects of oral curcumin on the post-MI LV systolic function are lower at 5 compared to 50 mg∙kg(-1)∙day(-1) and disappear at 0.5 mg∙kg(-1)∙day(-1). To clinically apply curcumin therapy for heart failure patients, a precise, optimal dose-setting study is required.

Diagnostic utility of unenhanced computed tomography for acute aortic syndrome.

BACKGROUND: The diagnostic value of unenhanced computed tomography (CT) for diagnosing acute aortic dissection (AAD) and ruptured thoracic aortic aneurysm (TAA) remains unclear. METHODS AND RESULTS: We examined 219 consecutive patients who visited the emergency room with suspected acute aortic syndrome (AAS) because of chest or back pain and who underwent both unenhanced and contrast-enhanced 64-row multi-detector CT. The unenhanced CT findings were evaluated by the cardiologist on duty who was blind to the findings of contrast-enhanced CT. Diagnosis of AAS was confirmed in 103 patients (47%, 95 AAD and 8 ruptured TAA patients) based on evaluation of both unenhanced and contrast-enhanced CT images, which was used as the reference standard for validating the diagnostic value of the unenhanced CT findings. Sensitivity and specificity of the findings of a high-attenuation crescent, which represents hematoma in the aortic wall, were 61.2% and 99.1%, respectively. Sensitivity and specificity of linear high density in the aorta, which represents an intimal flap, were 59.2% and 96.6%, respectively. If unenhanced CT showed none of high-attenuation crescent, linear high density, internal displacement of intimal calcification, or TAA, the negative predictive value was 93.3%. CONCLUSIONS: Unenhanced CT is a good tool for ruling AAS in, but the false-negative rate of 6.7% is high for ruling AAS out because it has to be the minimum possible.