Synthetic ditempolphosphatidylcholine liposome-like nanoparticles for anti-oxidative therapy of atherosclerosis.

Atherosclerosis (AS), a chronic inflammatory disease, is the leading cause of death worldwide. Anti-oxidative therapy has been developed for AS therapy in light of the critical role of ROS in pathogenesis of AS, but current anti-oxidants have exhibited limited outcomes in the clinic. Herein, new ROS-eliminating liposome-like NPs (Tempol-Lips) were assembled from synthetic lipids that covalently conjugated two Tempol molecules with phosphatidylcholine by esterification reaction. The obtained Tempol-Lips can be efficiently internalized into inflammatory macrophages and attenuated inflammation via scavenging overproduced intracellular ROS. After i.v. administration, Tempol-Lips with nanoscale character accumulated in the plaques of ApoE-/- mice through passive targeting and significantly inhibited the pathogenesis of AS, compared with those treated with control drugs. The therapeutic benefits of Tempol-Lips primarily are ascribed to the reduced local and systematic oxidative stress and inflammation. Preliminary studies in vivo further demonstrated Tempol-Lips were safe and biocompatible after long-term i.v. injection. Conclusively, Tempol-Lips can be developed as a novel anti-AS nanotherapy with potential translation in the clinic.

New Discovery of Left Atrial Macroreentry Tachycardia: Originating from the Spontaneous Scarring of Left Atrial Anterior Wall.

AIMS: This study sought to describe left atrial macroreentry tachycardia (LAMRT) originating from the spontaneous scarring of left atrial anterior wall (LAAW) and its clinical and electrophysiological characteristics, mechanisms, and the formation of substrates. METHODS AND RESULTS: 9 of 123 patients (89% female, age 79.78 ± 5.59 years) had LAMRT originating from the LAAW with no cardiac surgery or prior left atrial (LA) ablation. The mean tachycardia cycle length (TCL) was 241.67 ± 38.00 milliseconds. Spontaneous scars areas and low voltage areas (LVAs) in the LAAW were found in all patients. Successful ablation of the critical isthmus caused termination of the LAMRT and was not inducible in all patients. Arrhythmogenic substrates of LAMRT were the spontaneous scars of LAAW, which matched with the aorta or/and pulmonary artery contact area. The area under the curve (AUC) of age and combination of gender and age for predicting the LAMRT originating from the LAAW were 0.918 and 0.951, respectively, with a cutoff value of ≥73.5 years of age and gender (female) predicting LAMRT with 88.9% sensitivity and 89% specificity. CONCLUSION: Combination of gender and age provides a simple and useful criterion to distinguish LAMRT from cavotricuspid isthmus- (CTI-) dependent atrial tachycardia in macroreentry atrial tachycardia (MRAT) in patients without a history of surgery or ablation. Aorta or/and pulmonary artery contacting LA may be related to spontaneous scars. Ablation the isthmus eliminated LAMRT in all patients.

Influences of age, gender, and circadian rhythm on deceleration capacity in subjects without evident heart diseases.

BACKGROUND: Deceleration capacity (DC) is a newly found predictor of mortality after myocardial infarction. Age-, gender-, and circadian rhythm-related differences in DC may limit its predictive value, which should be considered in clinical settings. METHODS: DC, average heart rate, and HRV parameters, including 24 hours, awaking state (15:00-20:00) and sleeping mode (00:00-05:00) strips from 24 hours Holter recordings in 636 subjects without heart diseases were examined. Heart rate variability was analyzed in time domains (standard deviation of all normal-to-normal intervals [SDNN], normal-to-normal RR intervals in all 5-minute segments [SDANN], and root mean square successive difference [RMSSD]). RESULTS: The DC, SDNN, SDANN, RMSSD, and heart rate decreased with age. Deceleration capacity was significantly lower in patients greater than 50 years of age. The largest decrease of SDNN, SDANN, and RMSSD occurred in patients 30-39 years of age. The values of SDNN, SDANN, and DC of women were lower than that of men in the young and middle-aged groups, but age-related decrease of DC in men was greater than that in women. Heart rate of women was significantly higher than that of men in younger subjects, especially in a sleeping mode. There were higher values of DC and RMSSD during sleeping than that during a waking state. CONCLUSIONS: The age, gender, and circadian rhythm may be useful when evaluating cardiac autonomic function and need to be considered when evaluating DC and HRV in clinical and scientific researches.

Identification of a novel de novo mutation associated with PRKAG2 cardiac syndrome and early onset of heart failure.

INTRODUCTION: The major structure elements of the AMP-activated protein kinase (AMPK) are α, ß, and γ sunbunits. Mutations in γ2 subunit (PRKAG2) have been associated with a cardiac syndrome including inherited ventricular preexcitation, conduction disorder and hypertrophy mimicking hypertrophic cardiomyopathy. The aim of the present study was to identify PRKAG2 syndrome among patients presenting with left ventricular hypertrophy (LVH). METHODS AND RESULTS: Nineteen unrelated subjects with unexplained LVH were clinically and genetically evaluated. Among 4 patients with bradycardia, manifestations of preexcitation were only found in a 19 year old male who also developed congestive heart failure 3 years later. Electrophysiological study of this case identified the coexistence of an AV accessory pathway and AV conduction defect. Histological analysis of his ventricular tissue isolated by biopsy confirmed excessive glycogen accumulation, prominent myofibrillar disarray and interstitial fibrosis. Direct sequencing of his DNA revealed a heterozygous mutation in PRKAG2 consisting of an A-to-G transition at nucleotide 1453 (c.1453A>G), predicting a substitution of a glutamic acid for lysine at highly-conserved residue 485 (p.Lys485Glu, K485E), which was absent in his unaffected family members and in 215 healthy controls. To assess the role of K485 in the structure and function of the protein, computational modeling calculations and conservation analyses were performed. Electrostatic calculations indicate that K485 forms a salt bridge with the conserved D248 residue in the AMPK ß subunit, which is critical for proper regulation of the enzyme, and the K485E mutant disrupts the connection. CONCLUSIONS: Our study identifies a novel de novo PRKAG2 mutation in a young, in which progression of the disease warrants close medical attention. It also underlines the importance of molecular screening of PRKAG2 gene in patients with unexplained LVH, ventricular preexcitation, conduction defect, and/or early onset of heart failure.

Incidence and clinical characteristics of postcardiac injury syndrome complicating cardiac perforation caused by radiofrequency catheter ablation for cardiac arrhythmias.

BACKGROUND: Postcardiac injury syndrome (PCIS) is a complication of a variety of cardiac injuries, of which small heart perforation is the etiology that is often unrecognized. We reported a series of patients with PCIS secondary to cardiac perforation during catheter ablation procedures. METHODS AND RESULTS: Out of 1728 radiofrequency catheter ablation procedures, 21 patients (1.2%) were complicated by echo-defined cardiac perforation not requiring surgical intervention. Among them, 6 patients (6/21, 28.6%) were diagnosed with PCIS secondary to cardiac perforation because they also developed pleural effusions (6/6, 100%) and fever (4/6, 66.7%) in addition to pericardial effusion/tamponade. Four patients with PCIS (4/6, 66.7%) and four patients without PCIS (4/15, 26.7%) underwent pericardial drainage but the drainage volume during the first 24 h was not significantly different (441.3±343.9 mL vs. 182.5±151.3 mL, P=0.248). In the 6 PCIS patients, pleural effusion was detected from 3 h to 4 days (median: 2 days) after ablation procedure, predominantly bilateral (66.7%) or left-sided if unilateral. Patients with PCIS were older (64.8±7.3 years vs. 45.9±14.8 years, P=0.0078), were more likely accompanied by hypertension (66.7% vs. 6.7%, P=0.0114) and had a prolonged hospital stay (34.2±15.8 days). CONCLUSIONS: More than 25% of patients with small cardiac perforation during catheter ablation may develop PCIS which can be masked by pericardial effusion/tamponade. This kind of PCIS is more likely associated with elder or hypertensive patients and is usually characterized by early onset of pleural effusion.

Unilateral pulmonary artery stenosis and late-onset cataract in an adult: a case of suspected congenital rubella syndrome.

Congenital rubella syndrome is characterized by the triad of deafness, cataract and cardiovascular malformations. The great majority of the cases in the literature have been usually diagnosed in infancy and childhood because of various defects at birth. However, we report a rare case of suspected congenital rubella syndrome in an adult with unilateral pulmonary artery stenosis and late-onset cataract.