Body Fat Distribution and Left Atrial Reverse Remodeling After Catheter Ablation for Atrial Fibrillation.

Background: Emerging evidence suggests a pathophysiological link between obesity and atrial fibrillation (AF). However, the contribution of body fat distribution to left atrial (LA) remodeling and its reversibility remain unclear in nonobese AF patients. Objectives: The purpose of this study was to investigate the association of body fat distribution with LA size and reverse remodeling (LARR). Methods: In total, 116 nonobese patients with AF (88 men, age 63 ± 11 years) who underwent first catheter ablation (CA) were included. Body fat distribution was assessed with bioelectrical impedance, and body fat percentage (BF%) and central fat percentage (CF%) were calculated. Patients were categorized by body size metrics (body mass index [BMI] and waist-to-hip [W/H] ratio) and fat parameters (BF% and CF%). Echocardiography was performed before and 6 months after CA. Multivariable logistic regression was used to examine the association between the 4 metrics (ie, BMI, W/H ratio, BF%, and CF%) and a lack of LARR (<15% reduction or increase in the LA volume index). Results: Body size metrics and adiposity measures were not independently associated with baseline LA size. Six months after CA, the higher W/H ratio and CF% groups exhibited persistent LA enlargement compared to their counterparts (both P < 0.01). In the multivariable analysis, W/H ratio and CF% were associated with a lack of LARR (adjusted ORs of 3.86 and 2.81 per 0.10 and 10% increase, respectively, both P < 0.01). The combined assessment of CF% with W/H ratio provided complementary risk stratification for persistent LA enlargement. Conclusions: Central adiposity was associated with a lack of LARR after CA, highlighting the importance of assessing body fat distribution even in nonobese patients.

Association of Atrial Fibrillation Progression With Left Atrial Functional Reserve and Its Reversibility.

BACKGROUND: Atrial fibrillation (AF) progression is closely related to heart failure occurrence, and catheter ablation carries a beneficial effect for heart failure prevention. Recently, particular attention has been given to left atrial (LA) function and functional reserve in the pathogenesis linking AF and heart failure, although its significance and reversibility is not well studied. METHODS AND RESULTS: We prospectively investigated 164 patients with AF with normal left ventricular systolic function and free from heart failure who underwent first catheter ablation and pre-/postprocedural echocardiography. Conventional and speckle-tracking echocardiography were performed at rest and during passive leg lifting to assess LA size, LA reservoir strain (LARS), and functional reserve calculated as passive leg lifting-LARS - rest-LARS. Patients were categorized into 3 AF subtypes: paroxysmal AF (N=95), persistent AF (PeAF; N=50), and long-standing persistent AF (LS-PeAF; N=19). The PeAF and LS-PeAF groups had larger LA size and reduced LARS compared with the paroxysmal AF group (all P<0.05). LA functional reserve was significantly impaired in the LS-PeAF group (P=0.003). In multivariable analysis, LS-PeAF and advanced age were significantly associated with impaired LA functional reserve. Among 149 patients with sinus rhythm 1 to 2 days after catheter ablation, LARS was significantly improved in both PeAF and LS-PeAF groups but was still lower than that in the paroxysmal AF group. Sinus rhythm restoration also led to amelioration of LA functional reserve in patients with LS-PeAF. CONCLUSIONS: AF progression was related to impaired LARS and LA functional reserve, and restoration of sinus rhythm might contribute to early LA reverse remodeling.

Prevalence, Associated Factors, and Echocardiographic Estimation of Left Atrial Hypertension in Patients With Atrial Fibrillation.

Background Elevated left atrial (LA) pressure predisposes individuals to the initiation and persistence of atrial fibrillation (AF), and LA hypertension is associated with AF recurrence after catheter ablation (CA). However, the exact frequency and factors associated with LA hypertension are unknown, and its noninvasive estimation is challenging. This study aimed to investigate the prevalence and determinants of LA hypertension in patients with AF who underwent first CA. Methods and Results We examined 183 patients with AF who underwent conventional and speckle-tracking echocardiography before CA to assess LA size, reservoir strain, and stiffness. Direct LA pressure was measured at the time of CA, and LA hypertension was defined as mean LA pressure >15 mm Hg. Thirty-three (18.0%) patients exhibited LA hypertension. Patients with LA hypertension had a significantly larger LA volume index (40.2 [28.4-52.1] versus 34.1 [26.9-42.4] mL/m2, P=0.025), reduced LA reservoir strain (15.1 [10.4-21.7] versus 22.7 [14.4-32.3] %, P=0.002) and increased LA stiffness (0.69 [0.34-0.99] versus 0.36 [0.24-0.54], P<0.001). Multivariable analyses showed that waist circumference, C-reactive protein level, LA reservoir strain, and LA stiffness were independently associated with LA hypertension (all P<0.05), while LA volume and E/e' ratio were not. Among echocardiographic parameters, receiver operating characteristic curve analysis identified LA stiffness as the best predictor of LA hypertension. Conclusions Approximately 20% of patients with AF who underwent CA had LA hypertension. Central obesity and inflammation might be involved in the pathophysiological mechanisms of LA hypertension, and echocardiography-derived LA stiffness may have clinical utility for the detection of LA hypertension before CA.

Prevalence of glucose metabolism disorders and its association with left atrial remodelling before and after catheter ablation in patients with atrial fibrillation.

AIMS: To investigate the exact prevalence of glucose metabolism disorders, and their impact on left atrial (LA) remodelling and reversibility in patients with atrial fibrillation (AF). METHODS AND RESULTS: We examined 204 consecutive patients with AF who underwent their first catheter ablation (CA). Oral glucose tolerance test was used to evaluate glucose metabolism disorders in 157 patients without known diabetes mellitus (DM). Echocardiography was performed before and 6 months after CA. Oral glucose tolerance test identified abnormal glucose metabolism in 86 patients [11 with newly diagnosed DM, 74 with impaired glucose tolerance (IGT) and 1 with impaired fasting glucose (IFG)]. Ultimately, 65.2% of patients had abnormal glucose metabolism. Diabetes mellitus group had the worst LA reservoir strain and LA stiffness (both P < 0.05), while there was no significant difference in baseline LA parameters between normal glucose tolerance (NGT) group and IGT/IFG group. The prevalence of LA reverse remodelling (≥15% decrease in the LA volume index at 6 months after CA) was significantly higher in NGT group compared with IGT/IFG and DM group (64.1 vs. 38.6 vs. 41.5%, P = 0.006). Both DM and IFG/IGT carry a significant risk of lack of LA reverse remodelling independent of baseline LA size and AF recurrence. CONCLUSION: Approximately 65% of patients with AF who underwent their first CA had abnormal glucose metabolism. Patients with DM had significantly impaired LA function compared with non-DM patients. Impaired glucose tolerance/IFG as well as DM carries significant risk of unfavourable LA reverse remodelling. Our observations may provide valuable information regarding the mechanisms and therapeutic strategies of glucose metabolism-related AF.

Epicardial fat accumulation and left heart remodelling in patients with chronic coronary syndrome.

Aims: Patients with chronic coronary syndrome (CCS) suffer from subsequent cardiovascular events, even after complete revascularization; thus, elucidation of the underlying pathophysiological mechanisms is required. Epicardial adipose tissue (EAT) is increasingly recognized as a metabolically active organ with a key role in the pathogenesis of metabolic-related cardiac diseases. The present study investigated the association between EAT burden and left heart remodelling in patients with CCS. Methods and results: We studied 267 CCS patients (210 men; 71 ± 9 years) with complete revascularization and normal left ventricular (LV) ejection fraction who underwent follow-up echocardiography. All patients underwent the measurement of EAT thickness and speckle-tracking analysis to evaluate LV global longitudinal strain (LVGLS) and left atrial (LA) phasic strain. The mean EAT thickness was 5.0 ± 1.8 mm. Age, sex, body mass index, and diabetes mellitus were independently associated with EAT thickness (all P < 0.05). Multivariable linear regression analysis demonstrated that EAT thickness was significantly associated with LV mass index, early diastolic mitral annular velocity, and LA conduit strain independent of age, sex, and cardiovascular risk factors (all P < 0.05). On the other hand, there was no relationship between EAT thickness and LV systolic parameters including LV ejection fraction and LVGLS. Conclusion: CCS patients with increased EAT thickness had unfavourable left heart remodelling. The assessment of EAT thickness by echocardiography may have clinical utility as a simple surrogate to aid in risk stratification for impaired left heart function in CCS patients.

Association of arterial properties with left ventricular morphology and function in the community.

OBJECTIVES: Arterial structural and functional remodeling is recognized as a key determinant of incident heart failure, although the contribution of arterial properties on left ventricular (LV) remodeling is not fully studied. Aortic dilatation is an early manifestation of arterial remodeling and estimated pulse wave velocity (ePWV) is emerging as a simple measure of arterial stiffness. This study aimed to characterize the association of aortic size and ePWV with LV morphology and function. METHODS: The study cohort consisted of 539 participants without overt cardiac disease who underwent extensive cardiovascular examination. Aortic root diameter was measured by two-dimensional echocardiography and ePWV was calculated from a regression equation using age and mean blood pressure. LV global longitudinal strain (LVGLS) was obtained by speckle-tracking echocardiography. RESULTS: Aortic root diameter and ePWV were correlated with LV mass index and LVGLS, while only ePWV was related to E / e' ratio. In multivariable analysis, aortic root diameter and ePWV were significantly related to LV mass index and LVGLS (all P  < 0.05), and the association of aortic root size and ePWV with LVGLS was independent of LV mass index and E / e' ratio. Individuals with both aortic root enlargement and increased ePWV had significantly larger LV mass index and reduced LVGLS compared with those either or those with normal aortic size and ePWV (both P  < 0.05). CONCLUSION: Aortic root size and ePWV were independently associated with unfavorable LV remodeling in individuals free of cardiac disease, which might provide useful information into the pathogenesis-linking arterial remodeling and heart failure.

Incidence of atrial functional tricuspid regurgitation and its correlation with tricuspid valvular deformation in patients with persistent atrial fibrillation.

Background: With the growing prevalence of atrial fibrillation (AF), concomitant atrial functional tricuspid regurgitation (FTR) is increasing. In this study, we aimed to elucidate the incidence of significant atrial FTR and its association with tricuspid valvular (TV) deformation in patients with persistent AF. Methods: We retrospectively enrolled 344 patients (73.0 ± 9.3 years, 95 female) with persistent AF who underwent 2-dimensional echocardiography. We excluded patients with left-sided heart disease, pulmonary hypertension treated with pulmonary vasodilators, and congenital heart disease. We defined significant TR as having TR ≥ moderate; and tricuspid annulus (TA) diameter, tethering height, and area were measured in all patients. Results: Among the study population, 80 (23.3%) patients had significant TR. TA diameter, tethering height, and area were significantly greater in the significant TR group (all p < 0.001). In multivariable analysis, TA diameter was independently associated with significant TR (odds ratio 1.1 per mm, p = 0.03), whereas TV tethering height was not. Receiver operating characteristic curve for significant TR exhibited the best predictive value of TA diameter indexed for body surface area [23 mm/m2; area under the curve (AUC) = 0.87] compared with absolute TA diameter (39 mm; AUC = 0.74) and TA diameter indexed for height (0.22 mm/cm; AUC = 0.80). Conclusion: Approximately 25% of patients with persistent AF had significant TR. The BSA-corrected TA diameter was strongly associated with significant TR, which might be helpful for predicting the development of significant TR and considering its therapeutic strategy in patients with persistent AF.

Association of less-contrast media with clinical factors in elective percutaneous coronary intervention.

Since the amount of contrast media during percutaneous coronary intervention (PCI) is closely related to the exacerbation of renal function, it should be important to reduce the dose of contrast media during PCI. The purpose of this retrospective study was to evaluate the association of less-contrast media with clinical factors in elective PCI. A total of 709 patients were divided into the less-contrast media group (n = 142) and the conventional-contrast media group (n = 567) according to the quintile of total contrast volume. Univariate and multivariate logistic regression analyses were performed to find associations between the clinical variables and the less-contrast media group. The intravascular ultrasound (IVUS) use rate in the study population was considerably high (94.9%). In multivariable logistic regression analysis, an eGFR < 30 mL/min/1.73 m2 without hemodialysis was significantly associated with the less-contrast media group [odds ratio (OR) 43.73, 95% confidence interval (CI) 14.05-136.09, P < 0.001]. Left main-left anterior descending artery lesion (OR 0.28, 95% CI 0.17-0.48, P < 0.001), bifurcation lesion (OR 0.39, 95% CI 0.16-0.92, P = 0.03), chronic total occlusion (OR 0.22, 95% CI 0.06-0.90, P = 0.03) were inversely associated with the less-contrast media group. In conclusion, complex lesion characteristics were inversely associated with the less-contrast media in elective PCI. Since operators could access patients' renal function before elective procedure, an eGFR < 30 mL/min/1.73 m2 was most significantly associated with the less-contrast media. Our results suggest the possibility that the amount of contrast media is controllable in current PCI under IVUS-guidance.

Intentional switch between 1.5-mm and 1.25-mm burrs along with switch between rotawire floppy and extra-support for an uncrossable calcified coronary lesion.

Rotational atherectomy (RA) is considered to be the last resort for a severely calcified coronary artery lesion. Severe complications such as vessel perforation or burr entrapment is closely associated with forceful burr manipulation during RA. The instructions for use of Rotablator (Boston Scientific, Marlborough, MA, USA) prohibit forceful burr manipulation when rotational resistance occurs. Nevertheless, RA operators tend to forcefully manipulate the burr if it cannot cross the lesion, because there has been no established strategy for an uncrossable lesion. We present a case with a severely calcified coronary lesion, which was uncrossable by a burr 1.5 mm with RotaWire Floppy (Boston Scientific). We intentionally switched 2 burrs (1.5-mm and 1.25-mm) and 2 RotaWires (Floppy and Extra-support) to cross the lesion. Uniquely, we downsized the burr (from 1.5-mm to 1.25-mm) initially for better penetration force, and upsized the burr (from 1.25-mm to 1.5-mm) finally for better contact to the calcification within the lesion. Our case suggests that 4 different types of combinations might work in a mutually complementary manner for an uncrossable calcified lesion. .

Crystal structure and molecular dynamics simulation of ubiquitin-like domain of murine parkin.

Parkin is the gene product identified as the major cause of autosomal recessive juvenile Parkinsonism (AR-JP). Parkin, a ubiquitin ligase E3, contains a unique ubiquitin-like domain in its N-terminus designated Uld which is assumed to be a interaction domain with the Rpn 10 subunit of 26S proteasome. To elucidate the structural and functional role of Uld in parkin at the atomic level, the X-ray crystal structure of murine Uld was determined and a molecular dynamics simulation of wild Uld and its five mutants (K27N, R33Q, R42P, K48A and V56E) identified from AR-JP patients was performed. Murine Uld consists of two alpha helices [Ile23-Arg33 (alpha1) and Val56-Gln57 (alpha2)] and five beta strands [Met1-Phe7 (beta1), Tyr11-Asp18 (beta2), Leu41-Phe45 (beta3), Lys48-Pro51 (beta4) and Ser65-Arg72 (beta5)] and its overall structure is essentially the same as that of human ubiquitin with a 1.22 A rmsd for the backbone atoms of residues 1-76; however, the sequential identity and similarity between both molecules are 32% and 63%, respectively. This close resemblance is due to the core structure built by same hydrogen bond formations between and within the backbone chains of alpha1 and beta1/2/5 secondary structure elements and by nearly the same hydrophobic interactions formed between the nonpolar amino acids of their secondary structures. The side chain NetaH of Lys27 on the alpha1 helix was crucial to the stabilization of the spatial orientations of beta3 and beta4 strands, possible binding region with Rpn 10 subunit, through three hydrogen bonds. The MD simulations showed the K27N and R33Q mutations increase the structural fluctuation of these beta strands including the alpha1 helix. Reversely, the V56E mutant restricted the spatial flexibility at the periphery of the short alpha2 helix by the interactions between the polar atoms of Glu56 and Ser19 residues. However, a large fluctuation of beta4 strand with respect to beta5 strand was induced in the R42P mutant, because of the impossibility of forming paired hydrogen bonds of Pro for Arg42 in wild Uld. The X-ray structure showed that the side chains of Asp39, Gln40 and Arg42 at the N-terminal periphery of beta3 strand protrude from the molecular surface of Uld and participate in hydrogen bonds with the polar residues of neighboring Ulds. Thus, the MD simulation suggests that the mutation substitution of Pro for Arg42 not only causes the large fluctuation of beta3 strand in the Uld but also leads to the loss of the ability of Uld to trap the Rpn 10 subunit. In contrast, the MD simulation of K48A mutant showed little influence on the beta3-beta4 loop structure, but a large fluctuation of Lys48 side chain, suggesting the importance of flexibility of this side chain for the interaction with the Rpn 10 subunit. The present results would be important in elucidating the impaired proteasomal binding mechanism of parkin in AR-JP.

Parallel and antiparallel dimers of magainin 2: their interaction with phospholipid membrane and antibacterial activity.

Magainin 2 (M2) forms pores by associating with several other M2 molecules in lipid membranes and shows antibacterial activity. To examine the effect of M2 dimerization on biological activity and membrane interaction, parallel and antiparallel M2 dimers were prepared from two monomeric precursors. Antibacterial and haemolytic activities were enhanced by dimerization. CD measurements showed that both dimers and monomers have an alpha-helical structure in the presence of lipid vesicles. Tryptophan fluorescence shift and KI quenching studies showed that all the peptides were more deeply embedded in acidic liposomes than in neutral liposomes. Experiments on dye-leakage activity and membrane translocation of peptides suggest that dimers and monomers form pores through lipid membranes, although the pore formation may be accompanied by membrane disturbance. Although dimerization of M2 increased the interaction activity with lipid membranes, no appreciable difference between the activities of parallel and antiparallel M2 dimers was observed.