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Background: The outcomes of catheter ablation for atrial fibrillation in adults with congenital heart disease are not well described., Methods: In a retrospective study of adult patients with congenital heart disease who underwent catheter ablation for atrial fibrillation between 2000 and 2020 at Mayo Clinic, procedural characteristics and outcomes were collected. The primary outcomes were atrial arrhythmia (AA) recurrence following a 3-month blanking period and repeat ablation. An arrhythmia clinical severity score was assessed pre- and post-ablation based on the duration of arrhythmia episodes, symptoms, cardioversion frequency, and antiarrhythmic drug use., Results: One hundred forty-five patients (age, 57±12 years; 28% female; 63% paroxysmal atrial fibrillation) underwent 198 ablations with a median follow-up of 26 months (interquartile range, 14-69). One hundred ten, 26, and 9 patients had simple, moderate, and complex congenital heart disease, respectively. All patients underwent pulmonary vein isolation, and non-pulmonary vein targets were ablated in 79 (54%). AA recurrence at 12 months was 37% (95% CI, 29%-45%). On univariate analysis, increasing left atrial volume index was associated with higher odds of AA recurrence (odds ratio, 1.03 [1.00-1.06] per 1 mL/m 2 increment; P =0.05). Noninducibility of atrial flutter was predictive of decreased odds of AA recurrence (odds ratio, 0.43 [0.21-0.90]; P =0.03). A second ablation was performed in 43 patients after a median of 20 (interquartile range, 8-37) months. Arrhythmia clinical severity scores improved following ablation, reflecting a decrease in symptoms, cardioversions, and antiarrhythmic drugs., Conclusions: Catheter ablation of atrial fibrillation is feasible and effective in patients with adult congenital heart disease and reduces symptoms. Recurrence of AA frequently requires repeat ablation., Competing Interests: Disclosures Dr Madhavan receives research funding from Boston Scientific, BMS/Pfizer, and Convatec, Inc; speaker honorarium from Biosense Webster; and she is on the steering committee of CERTITUDE Registry, Biotronik, Inc. Dr Asirvatham receives speaking/honoraria from Abbott, Biosense Webster, Biotronik, Boston Scientific, Medtronic, and Zoll. All other authors have no conflicts to disclose.

Background: There are good data to support using a single high-sensitivity cardiac troponin T (hs-cTnT) below the limit of detection of 5 ng/L to exclude acute myocardial infarction. Per the US Food and Drug Administration, hs-cTnT can only report to the limit of quantitation of 6 ng/L, a threshold for which there are limited data. Our goal was to determine whether a single hs-cTnT below the limit of quantitation of 6 ng/L is a safe strategy to identify patients at low risk for acute myocardial injury and infarction., Methods: The efficacy (proportion identified as low risk based on baseline hs-cTnT<6 ng/L) of identifying low-risk patients was examined in a multicenter (n=22 sites) US cohort study of emergency department patients undergoing at least 1 hs-cTnT (CV Data Mart Biomarker cohort). We then determined the performance of a single hs-cTnT<6 ng/L (biomarker alone) to exclude acute myocardial injury (subsequent hs-cTnT >99th percentile in those with an initial hs-cTnT<6 ng/L). The clinically intended rule-out strategy combining a nonischemic ECG with a baseline hs-cTnT<6 ng/L was subsequently tested in an adjudicated cohort in which the diagnostic performance for ruling out acute myocardial infarction and safety (myocardial infarction or death at 30 days) were evaluated., Results: A total of 85 610 patients were evaluated in the CV Data Mart Biomarker cohort, among which 24 646 (29%) had a baseline hs-cTnT<6 ng/L. Women were more likely than men to have hs-cTnT<6 ng/L (38% versus 20%, P <0.0001). Among 11 962 patients with baseline hs-cTnT<6 ng/L and serial measurements, only 1.2% developed acute myocardial injury, resulting in a negative predictive value of 98.8% (95% CI, 98.6-99.0) and sensitivity of 99.6% (95% CI, 99.5-99.6). In the adjudicated cohort, a nonischemic ECG with hs-cTnT<6 ng/L identified 33% of patients (610/1849) as low risk and resulted in a negative predictive value and sensitivity of 100% and a 30-day rate of 0.2% for myocardial infarction or death., Conclusions: A single hs-cTnT below the limit of quantitation of 6 ng/L is a safe and rapid method to identify a substantial number of patients at very low risk for acute myocardial injury and infarction.

Objective: Triadin is a component of the calcium release complex of cardiac and skeletal muscle. Our objective was to analyze the skeletal muscle phenotype of the triadin knockout syndrome., Methods: We performed clinical evaluation, analyzed morphologic features by light and electron microscopy, and immunolocalized triadin in skeletal muscle., Results: A 6-year-old boy with lifelong muscle weakness had a triadin knockout syndrome caused by compound heterozygous null mutations in triadin. Light microscopy of a deltoid muscle specimen shows multiple small abnormal spaces in all muscle fibers. Triadin immunoreactivity is absent from type 1 fibers and barely detectable in type 2 fibers. Electron microscopy reveals focally distributed dilation and degeneration of the lateral cisterns of the sarcoplasmic reticulum and loss of the triadin anchors from the preserved lateral cisterns., Conclusions: Absence of triadin in humans can result in a congenital myopathy associated with profound pathologic alterations in components of the sarcoplasmic reticulum. Why only some triadin-deficient patients develop a skeletal muscle phenotype remains an unsolved question., (© 2017 American Academy of Neurology.)

Background: Long-QT syndrome (LQTS) may result in syncope, seizures, or sudden cardiac arrest. Although 16 LQTS-susceptibility genes have been discovered, 20% to 25% of LQTS remains genetically elusive., Methods and Results: We performed whole-exome sequencing child-parent trio analysis followed by recessive and sporadic inheritance modeling and disease-network candidate analysis gene ranking to identify a novel underlying genetic mechanism for LQTS. Subsequent mutational analysis of the candidate gene was performed with polymerase chain reaction, denaturing high-performance liquid chromatography, and DNA sequencing on a cohort of 33 additional unrelated patients with genetically elusive LQTS. After whole-exome sequencing and variant filtration, a homozygous p.D18fs*13 TRDN-encoded triadin frameshift mutation was discovered in a 10-year-old female patient with LQTS with a QTc of 500 milliseconds who experienced recurrent exertion-induced syncope/cardiac arrest beginning at 1 year of age. Subsequent mutational analysis of TRDN revealed either homozygous or compound heterozygous frameshift mutations in 4 of 33 unrelated cases of LQTS (12%). All 5 TRDN-null patients displayed extensive T-wave inversions in precordial leads V1 through V4, with either persistent or transient QT prolongation and severe disease expression of exercise-induced cardiac arrest in early childhood (≤3 years of age) and required aggressive therapy. The overall yield of TRDN mutations was significantly greater in patients ≤10 years of age (5 of 10, 50%) compared with older patients (0 of 24, 0%; P=0.0009)., Conclusions: We identified TRDN as a novel underlying genetic basis for recessively inherited LQTS. All TRDN-null patients had strikingly similar phenotypes. Given the recurrent nature of potential lethal arrhythmias, patients fitting this phenotypic profile should undergo cardiac TRDN genetic testing., (© 2015 American Heart Association, Inc.)

Progress in the modification of conventional coronary risk factors and lifestyle behavior has reduced the incidence of atherosclerotic coronary artery disease; nonetheless, it continues to be the leading cause of mortality in the world. This might be attributed to the defective risk stratifying and prevention strategy for coronary artery disease. In the current clinical setting, atherosclerotic coronary artery disease risk is estimated on the basis of identifying and quantifying only traditional risk factors; it does not take into consideration nontraditional risk factors. In addition, most of the prevailing therapies for atherosclerosis are targeted toward traditional risk factors rather than atherosclerosis itself. It is desirable to develop a method that can directly assess the activity of atherogenesis at every moment. Endothelial function is an integrated index of all atherogenic and atheroprotective factors present in an individual including nontraditional factors and heretofore unknown factors, and it is reported to have additional predictive value for future cardiovascular events to traditional risk factors. Moreover, endothelial function has a pivotal role in all phases of atherosclerosis, from initiation to atherothrombotic complication, and is reversible at every phase, indicating that endothelial function-guided therapies might be effective and feasible in cardiovascular practice. Thus, the introduction of endothelial function testing into clinical practice might enable us to innovate individualized cardiovascular medicine. In this review, we summarize the current knowledge on the contribution of endothelial dysfunction to atherogenesis and review the methods that assess endothelial function. Finally, we focus on the effects of major antiatherosclerotic disease therapies on endothelial function and argue the possibility of noninvasive assessment of endothelial function aiming at individualized cardiovascular medicine.

Objectives: We will provide a context to health information technology systems (HIT) safety hazards discussions, describe how electronic health record-computer prescriber order entry (EHR-CPOE) simulation has already identified unrecognized hazards in HIT on a national scale, helping make EHR-CPOE systems safer, and we make the case for all stakeholders to leverage proven methods and teams in HIT performance verification., Methods: A national poll of safety, quality improvement, and health-care administrative leaders identified health information technology safety as the hazard of greatest concern for 2013. Quality, HIT, and safety leaders are very concerned about technology performance risks as addressed in the Health Information Technology and Patient Safety report of the Institute of Medicine; and these are being addressed by the Office of the National Coordinator of HIT of the U.S. Dept. of Human Services in their proposed plans. We describe the evolution of postdeployment testing of HIT performance, including the results of national deployment of Texas Medical Institute of Technology's electronic health record computer prescriber order entry (TMIT EHR-CPOE) Flight Simulator verification test that is addressed in these 2 reports, and the safety hazards of concern to leaders., Results: A global webinar for health-care leaders addressed the top patient safety hazards in the areas of leadership, practices, and technologies. A poll of 76 of the 221 organizations participating in the webinar revealed that HIT hazards were the participants' greatest concern of all 30 hazards presented. Of those polled, 89% rated HIT patient/data mismatches in EHRs and HIT systems as a 9 or 10 on a scale of 1 to 10 as a hazard of great concern. Review of a key study of postdeployment testing of the safety performance of operational EHR systems with CPOE implemented in 62 hospitals, using the TMIT EHR-CPOE simulation tool, showed that only 53% of the medication orders that could have resulted in fatalities were detected. The study also showed significant variability in the performance of specific EHR vendor systems, with the same vendor product scoring as high as a 75% detection score in one health-care organization, and the same vendor system scoring below 10% in another health-care organization., Conclusions: HIT safety hazards should be taken very seriously, and the need for proven, robust, and regular postdeployment performance verification measurement of EHR system operations in every health-care organization is critical to ensure that these systems are safe for every patient. The TMIT EHR-CPOE flight simulator is a well-tested and scalable tool that can be used to identify performance gaps in EHR and other HIT systems. It is critical that suppliers, providers, and purchasers of health-care partner with HIT stakeholders and leverage the existing body of work, as well as expert teams and collaborative networks to make care safer; and public-private partnerships to accelerate safety in HIT. A global collaborative is already underway incorporating a "trust but verify" philosophy.

Background: Functional tricuspid regurgitation (FTR) with structurally normal valve is of poorly defined mechanisms. Prevalence and clinical context of idiopathic FTR (Id-FTR) (without overt TR cause) are unknown., Methods and Results: To investigate prevalence, clinical context, and mechanisms specific to FTR types, Id-FTR versus pulmonary hypertension-related (PHTN-FTR, systolic pulmonary pressure ≥50 mm Hg), we analyzed 1161 patients with prospectively quantified TR. Id-FTR (prevalence 12%) was associated with aging and atrial fibrillation. For mechanistic purposes, we measured valvular and right ventricular (RV) remodeling in 141 Id-FTR matched to 140 PHTN-FTR and to 99 controls with trivial TR for age, sex, atrial fibrillation, and ejection fraction. PHTN-FTR and Id-FTR were also matched for TR effective-regurgitant-orifice (ERO). Id-FTR valvular alterations (versus controls) were largest annular area (3.53±0.6 versus 2.74±0.4 cm(2), P<0.0001) and lowest valvular/annular coverage ratio (1.06±0.1 versus 1.45±0.2, P<0.0001) but normal valve tenting height. PHTN-FTR had mild annular enlargement but excessive valve tenting height (0.8±0.3 versus 0.35±0.1 cm, P<0.0001). Valvular changes were linked to specific RV changes, largest basal dilatation, and normal length (RV conical deformation) in Id-FTR versus longest RV with elliptical/spherical deformation in PHTN-FTR. With increasing FTR severity (ERO ≥40 mm(2)), changes specific to each FTR type were accentuated, and RV function (index of myocardial performance) was consistently reduced., Conclusions: Id-FTR is frequent, linked to aging and atrial fibrillation, can be severe, and is of unique mechanism. In Id-FTR, excess annular and RV-basal enlargement exhausts valvular/annular coverage reserve, and RV conical deformation does not cause notable valvular tenting. Conversely, PHTN-FTR is determined by valvular tethering with tenting linked to RV elongation and elliptical/spherical deformation. These specific FTR-mechanisms may be important in considering surgical correction in FTR.

We describe two cases of trisomy 2. The first case is a child with mosaic trisomy 2 who presented with mental retardation, multiple congenital anomalies, and dysmorphic findings similar to Pallister-Killian syndrome. The second case was an acardiac and acranial fetus with complete trisomy 2. We review the phenotypic spectrum associated with trisomy 2.

Background: Despite a nonobstructive coronary angiogram, many patients may still have an abnormal coronary vasomotor response to provocation and to myocardial demand during stress. The ability of noninvasive stress tests to predict coronary vasomotor dysfunction in patients with nonobstructive coronary artery disease is unknown., Methods and Results: All patients with nonobstructive coronary artery disease who had invasive coronary vasomotor assessment and a noninvasive stress test (exercise ECG, stress echocardiography, or stress nuclear imaging) within 6 months of the cardiac catheterization with provocation at our institution were identified (n=376). Coronary vasomotor dysfunction was defined as a percentage increase in coronary blood flow of

Background: Smoking is a major risk factor for cardiovascular events. One of the potential mechanisms may be related to both coronary endothelial dysfunction and increased inflammatory response. The present study was designed to test the hypothesis that smoking is associated with epicardial coronary endothelial dysfunction and inflammation., Methods and Results: Coronary endothelial function in response to acetylcholine was assessed in 881 patients (115 current smokers and 766 nonsmokers, including 314 previous smokers). Smokers were significantly younger than nonsmokers (43+/-1 versus 51+/-1 years, P<0.0001), had more epicardial vasoconstriction in response to intracoronary acetylcholine (-19+/-2% versus -14+/-1% change in coronary artery diameter, P=0.03), and were more likely than nonsmokers to have epicardial endothelial dysfunction (46% versus 35%, P=0.005), but their microvascular endothelial function was intact. Smokers had higher white blood cell counts than nonsmokers (7.7+/-0.2 versus 6.6+/-0.1x10(9)/L, P<0.0001), higher myeloperoxidase (156+/-19 versus 89+/-8 ng/mL), higher lipoprotein-associated phospholipase A2 (242+/-12 versus 215+/-5 ng/mL), and higher levels of intracellular adhesion molecule (283+/-14 versus 252+/-5 ng/mL). There were no differences in the levels of C-reactive protein, fibrinogen, or vascular cell adhesion molecule between the groups., Conclusions: Young smokers are characterized by epicardial coronary endothelial dysfunction, preserved microvascular endothelial function, and increased levels of inflammatory biomarkers and oxidative stress. The present study provides further information regarding the potential mechanisms by which smoking contributes to cardiovascular events.

Chronic ulcerative colitis (CUC) is associated with extraintestinal manifestations such as primary sclerosing cholangitis (PSC). The onset of PSC can precede the diagnosis of CUC, and require liver transplantation in some patients. Surgical management of CUC posttransplant has traditionally been open total proctocolectomy and ileal pouch-anal anastomosis. Herein, we present a case of a woman with a previous liver transplant for PSC who subsequently developed CUC with dysplasia, successfully treated with hand-assisted laparoscopic total proctocolectomy and ileal pouch-anal anastomosis. Hand-assisted laparoscopic surgery is an excellent option for patients with previous complex abdominal surgery. It can be performed safely and expediently, providing the benefits of reduced hospital stay and early return of bowel function.

Background: Although few studies have been performed recently, several have suggested that some practitioners are not well able to detect preset anesthesia machine faults., Methods: We performed a prospective study to determine whether there is a correlation between duration of anesthesia practice and the ability to detect anesthesia machine faults. Our hypothesis was that more anesthesia practice would increase the ability to detect anesthesia machine faults. This study was performed during a nationally attended anesthesia meeting held at a large academic medical center, where 87 anesthesia providers were observed performing anesthesia machine checkouts. The participants were asked to individually check out an anesthesia machine with an unspecified number of preset faults. The primary outcome measures were the written listing of faults detected during an anesthesia machine checkout., Results: Of the five faults preset into the test machine, participants with 0-2 yr experience detected a mean of 3.7 faults, participants with 2-7 yr experience detected a mean of 3.6 faults, and participants with more than 7 yr experience detected a mean of 2.3 faults (P < 0.001)., Conclusions: Our prospective study demonstrated that anesthesia machine checkout continues to be a problem.

Objective: The purpose of the current study was to determine whether lipoprotein-associated phospholipase A2 (Lp-PLA2) is associated with coronary endothelial dysfunction and is a predictor of endothelial dysfunction in humans., Methods and Results: Patients (172) with no significant coronary artery disease (<30% stenosis) undergoing assessment of coronary endothelial function were studied. Endothelial function was assessed by the change in coronary blood flow and coronary artery diameter in response to intracoronary acetylcholine. Plasma concentrations of Lp-PLA2 were measured, and patients were divided into tertiles. Patients in tertiles 2 and 3 had a significantly lower change in coronary blood flow (63.8+/-73.2 and 32.0+/-71.7 versus 78.4+/-73.2%; P<0.001) and greater epicardial coronary artery vasoconstriction (-14.1+/-14.7 and -23.3+/-25.1 versus -9.5+/-15.2% mean diameter change; P<0.001) in response to acetylcholine. Patients with coronary endothelial dysfunction had significantly higher serum concentrations of Lp-PLA2 than those with normal endothelial function (246.2+/-71.6 versus 209+/-56.7 ng/mL; P=0.001). The odds ratio for coronary endothelial dysfunction in patients with Lp-PLA2 in the highest tertile was 3.3 (95% CI, 1.6 to 6.6)., Conclusions: Lp-PLA2 is independently associated with coronary artery endothelial dysfunction and is a strong predictor of endothelial dysfunction in humans.