Value of multislice computed tomography angiography of the thorax in preparation for catheter ablation for the treatment of atrial fibrillation: the impact of unexpected cardiac and extracardiac findings on patient care

Objective

In patients referred for catheter ablation for the treatment of atrial fibrillation, multislice computed tomography angiography of the thorax is routinely performed to assess pulmonary vein anatomy. We sought to investigate the incidence of unexpected cardiac and extracardiac findings in this select patient population and to establish how these findings influence subsequent patient care.

Methods

Ninety-five patients (mean age 62 ± 10 years, 35% female) referred to our institution for ablation therapy for atrial fibrillation between July 2003 and October 2007 underwent multislice computed tomography angiography of the thorax. Radiologists interpreted all images. Need for additional testing, consultation and eventual diagnosis were assessed by electronic record review.

Results

A total of 83 (5 cardiac, 78 extracardiac) unexpected findings were observed in 50/95 (53%) of patients. The findings prompted 23 additional tests (5 cardiac, 18 noncardiac) in 15/95 (16%) of patients and 8 subsequent referrals in 7/95 (7%) patients. In 6 patients the findings significantly altered future patient care and resulted in postponement of ablation therapy in 4 patients. In 2 patients, extracardiac findings (pulmonary emboli and adenocarcinoma of the lung) were of potentially life-saving consequence.

Conclusions

In patients undergoing multislice computed tomography angiography of the thorax in anticipation of planned catheter ablation therapy for the treatment of atrial fibrillation, unexpected findings are common and of potentially significant value. In comparison, there is a higher prevalence of unexpected extracardiac, rather than cardiac findings. Further investigation of these findings may lead to postponement of ablation therapy, but may also be of potentially lifesaving consequence.     

Relationship of angiotensin-converting enzyme gene polymorphism with nephropathy associated with Type 2 diabetes mellitus in Asian Indians

OBJECTIVE: Diabetic nephropathy (DN) has become the leading cause of end-stage renal disease, but the pathogenesis of this condition is not exactly understood. Several studies from different parts of the world have examined angiotensin-converting enzyme (ACE) gene polymorphism as a candidate for DN. Two studies yielding controversial results have been reported from India. To rule out this discrepancy, we carried out a hospital-based study on a cohort from our population to determine whether ACE gene polymorphism is associated with DN. RESEARCH DESIGN AND METHODS: ACE gene polymorphism was analyzed by polymerase chain reaction in 460 individuals consisting of 174 cases of DN, 175 cases of Type 2 diabetes mellitus (DM), and 111 controls. The DN cases included in the study were Type 2 DM cases with serum creatinine >1.5 mg/dl and serum albumin >30 mg/dl in a 24-h urine sample. RESULTS: ACE insertion/deletion genotyping analysis showed DD genotype in 22.75% of DN cases, 15.42% of Type 2 DM cases, and 21.62% of controls. Chi-square test between the DN group and the control group did not show a significant difference in D allele. However, the difference was significant at P<.05 between the DN group and the DM group. The odds ratio was 2.0953 (95% confidence interval=1.35-3.2522), indicating a significant association of DD genotype and D allele with DN. CONCLUSION: Our data enable us to conclude that Asian Indians with D allele and Type 2 DM are at greater risk for developing DN.     

Atrial fibrillation ablation in cor triatriatum: value of intracardiac echocardiography

A 72-year old male, referred for percutaneous atrial fibrillation ablation, was found to have cor triatriatum during routine, pre-procedural transesophageal echocardiography. Accessing the superior pulmonary venous atrium and wide area circumferential ablation was guided by intracardiac echocardiography and performed without complications. The patient remains symptom-free, off anti-arrhythmic drug therapy, for 6 months following ablation. In this report, we emphasize the value of using intracardiac echocardiography during catheter ablation in patients with cor triatriatum.     

Pathways to dewetting in hydrophobic confinement

Liquid water can become metastable with respect to its vapor in hydrophobic confinement. The resulting dewetting transitions are often impeded by large kinetic barriers. According to macroscopic theory, such barriers arise from the free energy required to nucleate a critical vapor tube that spans the region between two hydrophobic surfaces—tubes with smaller radii collapse, whereas larger ones grow to dry the entire confined region. Using extensive molecular simulations of water between two nanoscopic hydrophobic surfaces, in conjunction with advanced sampling techniques, here we show that for intersurface separations that thermodynamically favor dewetting, the barrier to dewetting does not correspond to the formation of a (classical) critical vapor tube. Instead, it corresponds to an abrupt transition from an isolated cavity adjacent to one of the confining surfaces to a gap-spanning vapor tube that is already larger than the critical vapor tube anticipated by macroscopic theory. Correspondingly, the barrier to dewetting is also smaller than the classical expectation. We show that the peculiar nature of water density fluctuations adjacent to extended hydrophobic surfaces—namely, the enhanced likelihood of observing low-density fluctuations relative to Gaussian statistics—facilitates this nonclassical behavior. By stabilizing isolated cavities relative to vapor tubes, enhanced water density fluctuations thus stabilize novel pathways, which circumvent the classical barriers and offer diminished resistance to dewetting. Our results thus suggest a key role for fluctuations in speeding up the kinetics of numerous phenomena ranging from Cassie–Wenzel transitions on superhydrophobic surfaces, to hydrophobically driven biomolecular folding and assembly.The favorable interactions between two extended hydrophobic surfaces drive numerous biomolecular and colloidal assemblies (1–5), and have been the subject of several theoretical, computational, and experimental inquiries (6–22). Examples include the association of small proteins to form multimeric protein complexes, of amphiphlic block copolymers, dendrimers, or proteins to form vesicular suprastructures, and of patchy colloidal particles into complex crystalline lattices (23–27). When two such hydrophobic surfaces approach each other, water between them becomes metastable with respect to its vapor at a critical separation, d_c, that can be quite large (8, 9, 28–30). For nanometer-sized surfaces at ambient conditions, d_c is proportional to the characteristic size of the hydrophobic object, whereas for micron-sized and larger surfaces, d_c ～ 1?μm (29, 30). However, due to the presence of large kinetic barriers separating the metastable wet and the stable dry states, the system persists in the wet state, and a dewetting transition is triggered only at much smaller separations ( ～ 1 nm) (13, 22, 28, 30).To uncover the mechanism of dewetting, a number of theoretical and simulation studies have focused on the thermodynamics as well as the kinetics of dewetting in the volume between two parallel hydrophobic surfaces that are separated by a fixed distance, d < d_c (8, 10–16, 18–21). These studies have highlighted that the bottleneck to dewetting is the formation of a roughly cylindrical, critical vapor tube spanning the region between the surfaces (11, 14, 15). A barrier in the free energetics of vapor tube formation as a function of tube radius is also supported by macroscopic interfacial thermodynamics, wherein the barrier arises primarily from a competition between the favorable solid–vapor and unfavorable liquid–vapor surface energies (Eq. 1 and Fig. 1). Thus, the classical mechanism for the dewetting transition prescribes that a vapor tube that spans the volume between the two surfaces must first be nucleated, and if the vapor tube is larger than a certain critical size, it will grow until the entire confined volume is dry (9).Open in a separate windowFig. 1.(A–C) Simulation snapshots of water (shown in red/white) in confinement between two square hydrophobic surfaces (shown in cyan) of size L = 4 nm that are separated by a distance of d = 20 Å; configurations highlighting (A) the liquid basin, (B) a cylindrical vapor tube of radius, r, that spans the confined region, and (C) the vapor basin are shown. In the front views, only one of the confining surfaces is shown. (D) Macroscopic theory predicts a free energetic barrier to vapor tube formation (Eq. 1), suggesting that a vapor tube larger than a critical size must be nucleated before dewetting can proceed.Although it has been recognized that water density fluctuations must play a crucial role in nucleating vapor tubes (14, 15), the precise mechanism by which these tubes are formed is not clear. To understand how vapor tubes are formed and to investigate their role in the dewetting process, here we use molecular simulations in conjunction with enhanced sampling methods (31, 32) to characterize the free energetics of water density fluctuations in the region between two nanoscopic hydrophobic surfaces. Such a characterization of water density fluctuations in bulk water and at interfaces has already provided much insight into the physics of hydrophobic hydration and interactions (5, 13, 31–44). In particular, both simulations and theory have shown that the likelihood of observing low-density fluctuations adjacent to extended hydrophobic surfaces is enhanced relative to Gaussian statistics (13, 31, 36–38, 42). Further, the intricate coupling between enhanced solvent fluctuations and dewetting kinetics has been highlighted by both coarse-grained (45–47) and atomistic simulations (48–51).Here we show that such enhanced water density fluctuations influence the pathways to dewetting in hydrophobic confinement by stabilizing isolated cavities adjacent to one of the confining surfaces with respect to vapor tubes. As the density in the confined region is decreased, the stability of isolated cavities relative to vapor tubes also decreases, and at a particular density, isolated cavities abruptly transition to vapor tubes. Surprisingly, for d?d_c, that is, separations for which dewetting is thermodynamically favorable, we find that the nascent vapor tubes formed from the isolated cavities are already larger than the corresponding critical vapor tubes predicted by classical theory. Because the newly formed vapor tube is supercritical, it grows spontaneously. Importantly, because the formation of this supercritical vapor tube involves a nonclassical pathway that circumvents the critical vapor tube altogether, the process entails a smaller free energetic cost. Our results thus point to smaller kinetic barriers to dewetting than predicted by macroscopic theory.     

MTHFR C677T gene mutation as a risk factor for arterial stroke: a hospital based study.

Elevated homocysteine level is an independent risk factor for ischemic stroke, thrombotic and cardiovascular diseases. The enzyme methylenetetrahydrofolate reductase (MTHFR) plays a crucial role in regulating the levels of homocysteine. A C677T mutation in this gene results in reduced activity. Sixty-nine patients with arterial stroke, six patients with venous stroke (confirmed by computed tomography and/or magnetic resonance imaging) with hyperhomocysteinemia were selected for the study. Forty-nine subjects with no past history of stroke served as controls. MTHFR genotypes were determined by PCR using specific primers, followed by restriction digestion and gel analysis. The prevalence of the mutated homozygous and heterozygous C677T MTHFR genotype in the patients with arterial stroke was 1.4% (one of 69) and 31.88% (21 of 69), respectively. There frequency was 16.6% (one of six) and 33.3% (two of six) in venous stroke. The genotyping results from controls showed that there was only one heterozygote out of the 49 studied (2.08%). There was a significant difference between the control and the patient groups. Odds ratio for the probability of the C677T MTHFR gene mutation in the patients versus control group was 22.29 (95% CI 4.89-98.8). This indicates that C677T MTHFR mutation is strongly associated with arterial stroke especially in young adults. MTHFR allele evaluation will help in preventing/reducing morbidity caused by stroke.     

Donor‐specific antibodies detected by single antigen beads alone can help risk stratify patients undergoing retransplantation across a repeat HLA mismatch

Whether reexposure to mismatched HLA antigens (RMM) in the setting of a negative crossmatch is associated with increased immunological risk remains an area of uncertainty. This is due to evidence derived predominantly from registry data, which lacks comprehensive information on alloantibody and rejection. In this study, we analyze the impact of low‐level preformed donor‐specific antibodies (DSA) against an RMM on transplant outcomes. From 1988 consecutive renal transplant recipients, we analyzed 179 patients undergoing retransplantation, of whom 55 had a RMM. All patients were crossmatch negative and preformed DSA were detected by single antigen beads alone. Multivariate analysis revealed that patients with preformed DSA against an RMM were independently at risk of antibody‐mediated rejection (HR 8.70 [3.42‐22.10], P < .0001) and death‐censored allograft loss (HR 3.08 [1.17‐8.14], P = .023). In addition, prior transplant nephrectomy (HR 2.04 [1.00‐4.17], P = .0495) was also associated with allograft failure, whereas receiving a retransplant that was matched at HLA class II was associated with a favorable outcome (HR 0.37 [0.14‐0.99], P = .047). In the absence of preformed DSA, an RMM was not associated with de novo DSA development, rejection, or allograft loss. In conclusion, an RMM portends increased immunological risk only in the presence of a preformed DSA in patients undergoing retransplantation.     

Left atrial reservoir function predicts atrial fibrillation recurrence after catheter ablation: a two-dimensional speckle strain study

Background  

Predictors of atrial fibrillation (AF) recurrence after catheter ablation (CA) are not fully defined. We hypothesized that 2D left atrial (LA) regional strain maps would help identify abnormal atrial substrate that increases susceptibility to AF recurrence post-CA.