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Background: Atrial fibrillation (AF) is the most common arrhythmia in patients with hypertrophic obstructive cardiomyopathy (HOCM). Data regarding the correlations of thyroid dysfunction and the incidence of AF in HOCM are quite limited. This study aimed to reveal the correlations between different thyroid status and the corresponding incidence of AF in a large HOCM cohort. Methods: A total of 806 HOCM patients with complete information on thyroid function tests and comprehensive cardiac evaluations were recruited. The participants were divided into the AF group (n = 159) and non-AF group (n = 647) according to established medical history and results of Holter monitoring. The thyroid status of the study population and the corresponding incidence of AF were assessed and analyzed. Results: Hypothyroidism accounted for the greatest proportion of thyroid dysfunction in HOCM patients. The incidence of AF significantly increased in individuals with both overt (P = 0.022) and subclinical (P = 0.007) hypothyroidism. Compared with participants in the non-AF group, those with positive AF episodes presented with lower free triiodothyronine (FT3) (2.86 ± 0.52 pg/mL vs. 3.01 ± 0.42 pg/mL, P = 0.001), higher free thyroxine (FT4) (1.24 ± 0.25 ng/dL vs. 1.15 ± 0.16 ng/dL, P < 0.001), and remarkably increased levels of thyrotropin (TSH) (12.6% vs. 5.3%, P = 0.001). Multivariable analyses demonstrated that the concentrations of FT3 (odds ratio [OR] = 0.470, 95% confidence interval [CI]: 0.272-0.813, P = 0.007) and FT4 (OR = 17.992, 95% CI: 5.750-56.296, P < 0.001), as well as TSH levels above normal ranges (OR = 2.276, 95% CI: 1.113-4.652, P = 0.024) were independently associated with the occurrence of AF in the large HOCM cohort. Conclusions: This study indicated a strong link between low thyroid function and the presence of AF in HOCM. Hypothyroidism (both overt and subclinical states) seems to be valuable for assessing the incidence of AF in patients with HOCM. Key words: Atrial fibrillation; Hypertrophic obstructive cardiomyopathy; Hypothyroidism; Thyroid hormone

BACKGROUND Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heritable myocardium disorder that predominantly affects the ventricle. Little is known about atrial involvement. This study aimed to assess atrial involvement, especially the role of genotype on atrium in ARVC. METHODS The incidence, characterization and predictors of atrial involvement were investigated. Nine known ARVC-causing genes were screened and the correlation between genotype and atrial involvement was assessed. RESULTS Right atrium (RA) dilation, left atrium (LA) dilation, and sustained atrial tachyarrhythmias (ATa) were found in 45, 16 and 3 patients, respectively. Gene mutations were identified in 64 (64.0%) patients. Mutation carriers showed more RA dilation than noncarriers (54.7% vs. 27.8%, P = 0.009), and no difference in LA dilation and ATa. Multivariate analysis showed tricuspid regurgitation (OR: 18.867; 95% CI: 1.466-250.000; P = 0.024) increased the risk of RA dilation and decreased left ventricular ejection fraction (LVEF) (OR: 1.134; 95% CI: 1.002-1.272; P = 0.031) correlated with LA dilation, whereas genotype showed no significant effect. At a median follow-up time of 91 months, 7 patients died and 1 patient accepted heart transplantation. New-onset RA dilation, LA dilation, and sustained ATa were found in 8, 7, and 6 patients, respectively. Atrial involvement was not associated with the long-term survival. Despite mutation carriers showing more RA dilation, Kaplan-Meier analysis showed genotype was not associated with atrial involvement. CONCLUSION Atrial involvement was common in ARVC. Tricuspid regurgitation and decreased LVEF increased the risk for atrial dilation. Genotype was not associated with atrial involvement.

In this paper, a rapid and sensitive flow injection-chemiluminescence (FI-CL) method is proposed for the quantitative determination of rutin based on the inhibitory effect of rutin on the chemiluminescence intensity from the luminol–chymotrypsin (CT) system. The decrease of CL intensity was found to be proportional to the logarithm of rutin concentration in the range 0.1–30.0 ng/mL. A method for the quantification of rutin is proposed, with the limit of detection (LOD) of 0.03 ng/mL (3σ). A complete analytical process including sampling and washing for rutin determination, which was conducted at a flow rate of 2.0 mL/min, could be performed completely within 30 s, yielding a sample efficiency of 120 h−1. The proposed procedure was successfully applied for the determination of rutin in human urine after oral intake, with recoveries varying from 93.9 to 108.1% and relative standard derivation

RFCA for Asymptomatic Persistent AFBackground Whether patients with asymptomatic atrial fibrillation (AF) could benefit from radiofrequency catheter ablation (RFCA) remains unclear. This study aimed to compare the outcomes of RFCA between asymptomatic and symptomatic AF. Methods Sixty-six patients with asymptomatic persistent AF who underwent the primary ablation for AF were enrolled; 132 patients with symptomatic persistent AF were matched using propensity score matching. All patients underwent circumferential pulmonary vein isolation in combination with linear ablation using AF termination as the primary procedural endpoint. Results Sinus rhythm (SR) was restored by ablation in 18 (27.3%) patients in the asymptomatic group and 93 (70.5%) in the symptomatic group (P < 0.001). Combined with intravenous infusion of ibutilide (1 mg), the numbers were 45 (68.2%) and 116 (87.8%), respectively (P = 0.001). At 1-year follow-up, SR was present in 23 (34.8%) patients in the asymptomatic group and 78 (59.1%) in the symptomatic group without any antiarrhythmic medication after a single procedure (P = 0.001). Of the 43 patients experiencing recurrence in the asymptomatic group, 16 (37.2%) had recurrent atrial tachycardia (AT)-related symptoms. Multivariate analysis showed that asymptomatic AF was independently associated with AF failed to be terminated by ablation (OR: 7.1; 95% CI: 3.4 to 14.9; P < 0.001) and recurrence (OR: 2.2; 95% CI: 1.1 to 4.4; P = 0.018). Patients with asymptomatic AF showed less improvement in quality of life postablation than those with symptoms. Conclusion Current catheter ablation techniques showed worse outcomes in asymptomatic AF patients than in those with symptoms. Recurrent AT could cause significant symptoms in previously asymptomatic patients.

A Cu-catalyzed asymmetric detrifluoroacetylative aldol addition reaction of 2-fluoro-1,3-diketones/hydrates to aldehydes in the presence of base and chiral bidentate ligand was developed. The reaction was carried out under convenient conditions and tolerated a wide range of substrates, resulting in fluorinated quaternary stereogenic α-fluoro-β-hydroxy ketone products with good chemical yields, diastereo- and enantioselectivities. This catalytic asymmetric detrifluoroacetylative aldol addition reaction provides a new approach for the preparation of biologically relevant products containing C-F quaternary stereogenic centers.

Intracardiac Thrombosis in ARVC Background Intracardiac thrombus has been reported in anecdotal cases of arrhythmogenic right ventricular cardiomyopathy (ARVC). This prospective study aimed to determine the prevalence, risk factors, and prognosis of intracardiac thrombosis in patients with ARVC. Methods From February 2004 to August 2013, transthoracic echocardiograms and magnetic resonance imagings were performed in 193 patients with ARVC. The prevalence, risk factors, and prognosis of intracardiac thrombosis were investigated. Results Ten intracardiac thrombi were identified in 8 patients (4.1%), the majority (7/10) of which were found in the right ventricular apex. Multivariate analysis showed that female gender and left ventricular dysfunction were independently associated with increased risk for thrombosis in ARVC. All thrombi were eliminated in 3 weeks after anticoagulation therapy without any complication. During a median follow-up time of 38 months (range 2 to 128), no thromboembolism event or sudden death was observed in patients under anticoagulation therapy; however, in patients without anticoagulation therapy, definite pulmonary thromboembolism occurred in 1 and sudden death due to suspected pulmonary thromboembolism was observed in another. Conclusion Intracardiac thrombosis may occur in certain patients with ARVC. Female gender and left ventricular dysfunction appeared to be associated with increased risk for thrombosis. Early screening and effective anticoagulation therapy may improve the prognosis.

This study describes the anomalous outcome of the Mannich-type reaction of N-tert-butylsulfinyl-3,3,3-trifluoroacetaldimine and Li derivatives of benzo[d]thiazoles, which offers a convenient and generalized method for the synthesis of biologically relevant (E)-1,2-bis(2-benzothiazolyl)ethanes. The mechanism, scope, and scalability of this new reaction are discussed.

Long-Term Follow-Up of Linear Ablation for AF Background The long-term outcome of radiofrequency catheter ablation in persistent atrial fibrillation (AF) patients remains controversial due to different procedural strategies. This study aimed to present the clinical outcome of a pure linear ablation approach without circumferential pulmonary vein isolation (CPVI) over an extended (>5 years) follow-up period. Methods From January 2005 to December 2009, 120 consecutive patients (94 men; age, 53.6 ± 10.3 years) with drug-refractory persistent AF that underwent pure linear ablation using AF termination as the desired procedural endpoint were enrolled. Results In the primary procedure, sinus rhythm was restored by ablation in 75 (62.5%) patients, and the remaining 45 patients in whom AF could not be terminated by ablation received electrical cardioversion. During a median follow-up period of 5.1 (range 3.2–7.5) years, sinus rhythm was maintained in 48 (40.0%) patients without any antiarrhythmic drugs after a single procedure. There was a higher long-term success in the patients in whom AF was terminated by ablation than in those requiring cardioversion (49.3 vs. 24.4%; P = 0.007). Conclusion Linear catheter ablation without CPVI is effective for persistent AF. Patients with AF terminated by ablation were associated with a better long-term outcome than those requiring cardioversion

(S)-N-(tert-Butylsulfinyl)-3,3,3-trifluoroacetaldimine underwent reactions with enolates of glycine esters with quite remarkable stereochemical results, that is, with virtually complete (>99 % de) diastereoselectivity and excellent (>98 %) yields. Furthermore, the reactions are conducted under operationally convenient conditions (Cs2CO3-catalyzed, ambient temperature) to provide the most advanced, general, and scalable access to biologically important β-trifluoromethylated α,β-diamino acids.

Reaction of 2-fluoro-1,3-diketone hydrates (I), (IV), and (VI) with aldehydes proceeds through a detrifluoroacetylative aldol addition mechanism to yield fluorinated aldol products in good stereoselectivities.

Herein is reported a study of asymmetric decarboxylative Mannich addition reactions between (Ss)-N-t-butylsulfinyl-3,3,3-trifluoroacetaldimine and Schiff bases derived from various aldehydes and lithium 2,2-diphenylglycinate. These reactions proceed with excellent diastereoselectivities and good chemical yields, providing a practical method for preparation of trifluoromethyl-containing vicinal diamines. The procedures can be conducted under convenient conditions, rendering this approach of high synthetic value.

Functionalization of the pyrrole ring using imine (II) as reagent takes place at position 3 of indoles (I) under Friedel—Crafts conditions, whereas position 2 of N-protected indoles (IV) is substituted in the presence of LDA.

A highly diastereoselective synthesis of a previously unknown type of aminobenzothiazol derivatives of high pharmaceutical potential is given.

The synthesis of a novel type of fluorinated sulfonamides with high pharmaceutical potential can be scaled up.

Enolates of indolin-2-ones react cleanly with the chiral imine (II) to afford adducts (III) and (V) in good diastereoselectivity.

CF3-containing chiral imines readily react with α,α-difluoroenolates affording a novel type of β-keto-amino compounds featuring the R-CO-CF2-CH(NH2)-CF3 moiety. The reactions feature exceptional generality allowing preparation of various aromatic, hetero-aromatic and aliphatic derivatives in high yields and diastereoselectivity. The products are configurationally stable and can be transformed to more functionalized complex compounds.

Here we describe the first attempts to scale up five addition reactions between (SS)-N-tert-butanesulfinyl-(3,3,3)-trifluoroacetaldimine 6 with C-nucleophiles derived from ketones (two examples), glycine Schiff base and heterocycles (two examples). In all cases studied, the observed stereochemical outcome of the scaled up (5.0–25.0 mmol) reactions was lower as compared with the original 0.5 mmol scale. However, the observed worsening of yields and diastereoselectivity was not identical and depended on the reaction conditions and reaction mechanisms. In general, scaling up of the reactions conducted at ambient temperatures presented no problems while the low-temperature (−78 °C) processes would require special equipment to provide strict maintenance of the reaction temperature to obtain the desirable outcome. Importantly, using procedures described here, series of biologically relevant compounds containing 2,2,2-trifluoro-1-(amino)ethyl [CF3 CH(NH2)-] pharmacophore unit can be prepared in enantiomerically pure form on up to 5 g scale, allowing their systematic biological studies.

The main feature of the synthesis of unexpected bis(benzothiazolyl)ethanes is the unusual role of CF3-imine, which serves as a precursor to the bridging ethylene moiety.

Compound (IIIa) can be further transformed to the corresponding β-amino alcohol by stereoselective reduction of its ketone moiety.

We demonstrate that reactions between various 1-indanones and (SS)-N-tert-butanesulfinyl-(3,3,3)-trifluoroacetaldimine, conducted in the presence of catalytic amounts of LDA, occur with virtually complete stereochemical outcome, offering reliable and generalized access to biologically relevant β-trifluoromethyl-β-amino indanone derivatives. The products can be isolated in diastereomerically pure form simply by washing the crude reaction mixture with hexanes, underscoring practicality of the present method.

In the title reaction, the N-tert-butylsulfinyl group serves not only as an efficient chiral auxiliary, but also as an amine protecting group.