Search

Background and aims The are geographic variations in the incidence and prevalence of primary biliary cholangitis (PBC). The aim was to explore whether clinical outcomes of patients within Western Europe differ according to geographical region. Methods Ursodeoxycholic acid-treated patients from European centers from the Global PBC database diagnosed from 1990 onwards were included. Patients with a time lag > 1 year from diagnosis to start of follow-up were excluded. Differences in baseline characteristics were studied according to North/South and East/West, whereas outcomes (transplant-free survival and decompensation) were studied with center latitude and longitude. Cox regression analyses were adjusted for age, sex, diagnosis year, biochemical markers, and cirrhosis as a time-dependent covariate. Results One thousand eight hundred seventy-eight patients were included, and there were no geographical differences in age or sex, with a mean age of 54 years and 89% female patients. Those in North Europe were more often of a moderately advanced/advanced Rotterdam biochemical stage (28.4%) compared with South Europe (20.6%). Additionally, they exhibited higher median alkaline phosphatase (2.0 ×ULN vs. 1.4 ×ULN) and transaminases. In multivariable analysis, there was a significant interaction between center latitude and longitude for decompensation (P < 0.001) and a trend for transplant-free survival, in which the Northwestern area demonstrated an increased risk for poor outcomes as compared to the reference (Paris). Conclusion We describe geographic variations in outcomes for patients across Europe from specialist centers in the Global PBC Study Group. Further study is important to explore the potential individual, environmental, and healthcare-related factors that may be contributors.

INTRODUCTION: In primary biliary cholangitis (PBC), bilirubin and alkaline phosphatase (ALP) are widely established as independent predictors of prognosis. Current treatment goals do not aim for normalization of surrogate markers because their association with survival has not been defined. METHODS: The patient cohort from the GLOBAL PBC Study Group was used, comprising of long-term follow-up data from European and North American centers. Ursodeoxycholic acid-treated and untreated patients with bilirubin levels ≤1 × upper limit of normal (ULN) at baseline or 1 year were included. The association of normal ALP with transplant-free survival was assessed in a subgroup with ALP ≤1.67 × ULN at 1 year. Optimal thresholds of bilirubin and ALP to predict liver transplantation (LT) or death were evaluated. RESULTS: There were 2,281 patients included in the time zero cohort and 2,555 patients in the 1-year cohort. The bilirubin threshold with the highest ability to predict LT or death at 1 year was 0.6 × ULN (hazard ratio 2.12, 95% CI 1.69-2.66, P < 0.001). The 10-year survival rates of patients with bilirubin ≤0.6 × ULN and >0.6 × ULN were 91.3% and 79.2%, respectively (P < 0.001). The risk for LT or death was stable below the bilirubin levels of 0.6 × ULN, yet increased beyond this threshold. Ursodeoxycholic acid-induced reduction in bilirubin below this threshold was associated with an 11% improvement in 10-year survival. Furthermore, ALP normalization was optimal, with 10-year survival rates of 93.2% in patients with ALP ≤ 1 × ULN and 86.1% in those with ALP 1.0-1.67 × ULN. DISCUSSION: Attaining bilirubin levels ≤0.6 × ULN or normal ALP are associated with the lowest risk for LT or death in patients with PBC. This has important implications for treatment targets.

INTRODUCTION: Comparative data on scores that predict outcome in primary biliary cholangitis (PBC) are scarce. We aimed to assess and compare the prognostic value of the Mayo Risk Score (MRS, 1989 and 1994), UK-PBC score, and GLOBE score in a large international cohort of patients with PBC. METHODS: Ursodeoxycholic acid-treated patients from 7 centers participating in the GLOBAL PBC Study Group were included. The discriminatory performance of the scores was assessed with concordance statistics at yearly intervals up to 5 years. Model for End-stage Liver Disease was included for comparison. Prediction accuracy was assessed by comparing predicted survival and actual survival in Kaplan-Meier analyses. RESULTS: A total of 1,100 ursodeoxycholic acid-treated patients with PBC were included, with a mean (SD) age of 53.6 (12.0) years, of whom 1,003 (91%) were female. During a median follow-up of 7.6 (interquartile range 4.1-11.7) years, 42 patients underwent liver transplantation, and 127 patients died. At 1 year, the concordance statistic for Model for End-stage Liver Disease was 0.68 (95% confidence interval [CI] 0.64-0.72), 0.74 (95% CI 0.67-0.80) for the UK-PBC score, 0.76 (95% CI 0.72-0.81) for the MRS (1989 and 1994), and 0.80 (95% CI 0.76-0.84) for the GLOBE score. The GLOBE score showed superior discriminatory performance, but differences were not statistically different. For all scores, discriminatory performance increased in those with bilirubin >0.6 × ULN and advanced fibrosis estimated with Fibrosis-4. The predicted (median) minus observed 5-year transplant-free survival was +0.4% and +2.5% for the MRS (1989) and GLOBE score, respectively. DISCUSSION: All prognostic scores developed for PBC (GLOBE, UK-PBC, and MRS) demonstrated comparable discriminating performance for liver transplantation or death as well as good prediction accuracy.

Objectives: To assess the safety and feasibility of early single‐dose mitomycin C (MMC) bladder instillation after robot‐assisted radical nephroureterectomy (RARNU) at a tertiary kidney cancer centre. RARNU with bladder cuff excision and subsequent MMC bladder instillation to reduce recurrence risk is the ‘gold standard’ for high‐risk upper urinary tract urothelial carcinoma (UUTUC). We adapted a RARNU technique with precise distal ureteric dissection, bladder cuff excision and watertight bladder closure. Patients and Methods: We retrospectively reviewed all patients undergoing RARNU for UUTUC at our centre performed as a standardised transperitoneal procedure comprising of: bladder cuff excision, two‐layer watertight closure and intraoperative bladder leak test; without re‐docking/re‐positioning of the robotic surgical system. Patient demographics, the timing of MMC instillation, adverse events (surgical and potentially MMC‐related) and length of stay (LOS) were assessed according to the Clavien–Dindo classification. Results: A total of 69 patients underwent a RARNU with instillation of MMC. The median (interquartile range [IQR]) age was 70 (62–78) years. The median (IQR) day of MMC instillation was 2 (1–3) days and the median (IQR) LOS was 2 (2–4) days, with urethral catheter removal on day of discharge in all cases. Only Grade I Clavien–Dindo complications occurred in seven patients (10%); five had ileus, one a wound infection and one a self‐limiting delirium, all managed conservatively. No adverse events potentially related to MMC instillation were noted within 30 days postoperatively. Conclusion: The use of intravesical MMC instillation given in the immediate postoperative period appears feasible and safe in patients undergoing RARNU with intraoperative confirmation of a water‐tight closure ensuring early catheter‐free discharge, with no significant adverse events. The potential reduction in intravesical recurrence in patients receiving early MMC needs to be assessed with longitudinal follow‐up studies.

The Fontan circulation has inherent long-term vulnerabilities such that adult Fontan patients now comprise the largest, most rapidly growing subgroup of adult congenital heart disease referred for transplant assessment. Almost all have Fontan Associated Liver Disease (FALD). There is an absence of mid to late hepatic outcome data after heart transplant alone . Therefore, we analyzed outcomes of survivors of heart only transplant in patients with failing Fontan circulation. Including all ten of our adult Fontan patients surviving >1 year after isolated heart transplant, we report evolution of their clinical features, bloodwork, hemodynamic data and liver ultrasound findings over a median of 4.7 years. Non-progression of FALD, resolution of ascites and freedom from hepatocellular carcinoma in the mid-term highlight the outcomes in this selected group once normal cardiac output and venous pressures are established by heart transplant.

Primary sclerosing cholangitis (PSC) represents a major unmet medical need. In a phase II double-blind, placebo-controlled study, we tested the safety and efficacy of cilofexor (formerly GS-9674), a nonsteroidal farnesoid X receptor agonist in patients without cirrhosis with large-duct PSC. Patients were randomized to receive cilofexor 100 mg (n = 22), 30 mg (n = 20), or placebo (n = 10) orally once daily for 12 weeks. All patients had serum alkaline phosphatase (ALP) > 1.67 × upper limit of normal and total bilirubin ≤ 2 mg/dL at baseline. Safety, tolerability, pharmacodynamic effects of cilofexor (serum C4 [7α-hydroxy-4-cholesten-3-one] and bile acids), and changes in liver biochemistry and serum fibrosis markers were evaluated. Overall, 52 patients were randomized (median age 43 years, 58% male, 60% with inflammatory bowel disease, 46% on ursodeoxycholic acid). Baseline median serum ALP and bilirubin were 348 U/L (interquartile range 288-439) and 0.7 mg/dL (0.5-1.0), respectively. Dose-dependent reductions in liver biochemistry were observed. At week 12, cilofexor 100 mg led to significant reductions in serum ALP (median reduction -21%; P = 0.029 versus placebo), gamma-glutamyl transferase (-30%; P < 0.001), alanine aminotransferase (ALT) (-49%; P = 0.009), and aspartate aminotransferase (-42%; P = 0.019). Cilofexor reduced serum C4 compared with placebo; reductions in bile acids were greatest with 100 mg. Relative reductions in ALP were similar between ursodeoxycholic acid-treated and untreated patients. At week 12, cilofexor-treated patients with a 25% or more relative reduction in ALP had greater reductions in serum alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, tissue inhibitor of metalloproteinase 1, C-reactive protein, and bile acids than nonresponders. Adverse events were similar between cilofexor and placebo-treated patients. Rates of grade 2 or 3 pruritus were 14% with 100 mg, 20% with 30 mg, and 40% with placebo. Conclusion: In this 12-week, randomized, placebo-controlled study, cilofexor was well tolerated and led to significant improvements in liver biochemistries and markers of cholestasis in patients with PSC.

Lassa fever (LF) is an acute viral haemorrhagic illness with various non-specific clinical manifestations. Neurological symptoms are rare at the early stage of the disease, but may be seen in late stages, in severely ill patients.The aim of this study was to describe the epidemiological evolution, socio-demographic profiles, clinical characteristics, and outcomes of patients seen during two Lassa fever outbreaks in Ebonyi State, between December 2017 and December 2018. Routinely collected clinical data from all patients admitted to the Virology Centre of the hospital during the period were analysed retrospectively. Out of a total of 83 cases, 70(84.3%) were RT-PCR confirmed while 13 (15.7%) were probable cases. Sixty-nine (83.1%) patients were seen in outbreak 1 of whom 53.6% were urban residents, while 19%, 15%, and 10% were farmers, students and health workers respectively. There were 14 (16.8%) patients, seen in second outbreak with 92.9% rural residents. There were differences in clinical symptoms, signs and laboratory findings between the two outbreaks. The case fatality rates were 29.9% in outbreak 1 and 85.7% for outbreak 2. Neurological features and abnormal laboratory test results were associated with higher mortality rate, seen in outbreak 2. This study revealed significant differences between the two outbreaks. Of particular concern was the higher case fatality during the outbreak 2 which may be from a more virulent strain of the Lassa virus. This has important public health implications and further molecular studies are needed to better define its characteristics., Author summary Neurological manifestations are uncommon in the early stages of Lassa Fever. In Ebonyi State, an unusual pattern was observed between two outbreaks that occurred quite close together in time but with distinctly different presentations. Previous studies on the 2018 outbreak focused on the first part of the outbreak between December 2017—May 2018. We therefore compared the two outbreaks and observed that patients in the second outbreak which occurred between August 2018-December 2018, presented with early neurological symptoms and a high mortality rate. This observation highlights the need for further evaluation and molecular studies.

Background: Fibrosis stage predicts prognosis in patients with chronic liver disease independent of aetiology, although its precise role in risk stratification in patients with primary biliary cholangitis (PBC) remains undefined. Aim: To assess the utility of baseline fibrosis stage in predicting long‐term outcomes in the context of biochemical risk stratification Methods: In a large and globally representative cohort of patients with PBC, liver biopsies performed from 1980 to 2014 were evaluated. The predictive ability of histologic fibrosis stage in addition to treatment response at 1 year (Toronto/Paris‐II criteria), as well as non‐invasive markers of fibrosis (AST/ALT ratio [AAR], AST to platelet ratio index [APRI], FIB‐4), for transplant‐free survival was assessed with Cox proportional‐hazards models. Results: There were 1828 patients with baseline liver biopsy. Advanced histologic fi‐ brosis (stage 3/4) was an independent predictor of survival in addition to non‐invasive measures offibrosis with the hazard ratios ranging from 1.59 to 2.73 (P < .001). Patients with advanced histologic fibrosis stage had worse survival despite biochemical treat‐ ment response, with a 10‐year survival of 76.0%‐86.6% compared to 94.5%‐95.1% depending on the treatment response criteria used. Poor correlations were observed between non‐invasive measures of fibrosis and histologic fibrosis stage. Conclusion: Assessment of fibrosis stage grants prognostic value beyond biochem‐ ical treatment response at 1 year. This highlights the need to incorporate fibrosis stage in individual risk stratification in patients with PBC, partly to identify those that may derive benefit from novel therapies.

BACKGROUND & AIMS: Primary biliary cholangitis (PBC) predominantly affects middle-aged women; there are few data on disease phenotypes and outcomes of PBC in men and younger patients. We investigated whether differences in sex and/or age at the start of ursodeoxycholic acid (UDCA) treatment are associated with response to therapy, based on biochemical markers, or differences in transplant-free survival. METHODS: We performed a longitudinal retrospective study of 4355 adults in the Global PBC Study cohort, collected from 17 centers across Europe and North America. Patients received a diagnosis of PBC from 1961 through 2014. We evaluated the effects of sex and age on response to UDCA treatment (based on GLOBE score) and transplant-free survival using logistic regression and Cox regression analyses, respectively. RESULTS: Male patients were older at the start of treatment (58.3±12.1 years vs 54.3±11.6 years for women; P

Studies evaluating physician adherence to guideline recommendations for implantable cardioverter defibrillator (ICD) therapy are sparse, and none exist for the application of appropriate-use criteria (AUC) in clinical practice. As part of a quality improvement initiative, a review of all ICD procedures was performed from January 1, 2015 to December 31, 2016 in Alberta, Canada, to evaluate the proportion of patients receiving appropriate ICD therapy and to identify reasons for nonadherence. Our device-implant process involves an electrophysiologist or implanting cardiologist evaluation, reminders of ICD eligibility criteria on the device requisition, and peer-review consensus. Implants were classified according to the 2008 American College of Cardiology/American Heart Association/Heart Rhythm Society (ACC/AHA/HRS) ICD guidelines, 2013 Canadian Cardiovascular Society (CCS) Cardiac Resynchronization Therapy (CRT) guidelines, and 2013 AUC. There were 1,300 ICD procedures performed, and the mean age was 63.8 ± 12.9 years; 79% were male; the mean ejection fraction was 0.32 ± 0.13, and 69% were for primary prevention. Among all implants,1% were discordant with American College of Cardiology/American Heart Association/Heart Rhythm Society (ACC/AHA/HRS) recommendations. Among CRT implants, 10% were inconsistent with Canadian Cardiovascular Society (CCS) recommendations. According to AUC, 92% of implants were appropriate. Reasons for nonadherence to ACC/AHA/HRS recommendations included QRS width120 msec (n = 3), LVEF0.35 (n = 2) and recent myocardial infarction (MI) (n = 1). The most common reason for nonadherence to AUC was the absence of criteria for classification (n = 57, 4%). In this population-based study, we found that a process of specialist evaluation, eligibility reminders on device forms, and peer-review consensus may improve adherence to guideline recommendations and AUC for ICD therapy.

Obesity is a global epidemic affecting chronic inflammatory diseases. Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease that can occur as an extraintestinal manifestation of inflammatory bowel disease (IBD). Previously we reported that patients with PSC who are obese have a higher risk of advanced liver disease. Currently it is unknown how obesity accelerates or worsens PSC. We evaluated the progression of PSC in an antigen-driven cholangitis mouse model of diet-induced obesity. Obesity was induced in our murine model of immune-mediated cholangitis (OVAbil). OVAbil mice were fed standard chow or high-fat/sucrose diet for twelve weeks followed by induction of biliary inflammation by OVA-specific T cell transfer. Histopathological damage in portal tracts was scored and serum collected. Neutralizing antibodies against IL-15 were administered daily until study termination. Obese mice developed exacerbated liver inflammation and damage. Immune cell phenotyping in liver revealed greater numbers of neutrophils and CD8+ T cells in obese mice. Higher levels of cytokines and chemokines were found in obese mice with cholangitis. Immuno-neutralizing antibodies against IL-15 greatly attenuated cholangitis in obese mice. Obesity exacerbated experimental PSC in part by overproduction of IL-15. Timely targeting of IL-15 may slow the progression of PSC.

Changes over time in the presenting features and clinical course of patients with primary biliary cholangitis are poorly described. We sought to describe temporal trends in patient and disease characteristics over a 44-year period across a large international primary biliary cholangitis cohort of 4,805 patients diagnosed between 1970 and 2014, from 17 centers across Europe and North America. Patients were divided into five cohorts according to their year of diagnosis: 1970-1979 (n = 143), 1980-1989 (n = 858), 1990-1999 (n = 1,754), 2000-2009 (n = 1,815), and ≥2010 (n = 235). Age at diagnosis, disease stage, response to ursodeoxycholic acid, and clinical outcomes were compared. Mean age at diagnosis increased incrementally by 2-3 years per decade from 46.9 ± 10.1 years in the 1970s to 57.0 ± 12.1 years from 2010 onward (P < 0.001). The female to male ratio (9:1) and antimitochondrial antibody positivity (90%) were not significantly variable. The proportion of patients presenting with mild biochemical disease (according to Rotterdam staging) increased from 41.3% in the 1970s to 72.2% in the 1990s (P < 0.001) and remained relatively stable thereafter. Patients with a mild histological stage at diagnosis increased from 60.4% (1970-1989) to 76.5% (1990-2014) (P < 0.001). Correspondingly, response to ursodeoxycholic acid according to Paris-I criteria increased; 51.7% in the 1970s and 70.5% in the 1990s (P < 0.001). Recent decades were also characterized by lower decompensation rates (18.5% in the 1970s to 5.8% in the 2000s, P < 0.001) and higher 10-year transplant-free survival (48.4%, 68.7%, 79.7%, and 80.1% for each respective cohort; P < 0.001). Conclusion: In recent decades, a pattern of primary biliary cholangitis presentation consistent with an older age at diagnosis alongside reduced disease severity has been noted; the observed trends may be explained by an increase in routine testing of liver function and/or a changing environmental trigger. (Hepatology 2018;67:1920-1930).

BACKGROUND AND OBJECTIVE: The purpose of this randomized, single-masked clinical trial is to explore whether cefazolin mixed with 2% lidocaine can reduce pain. PATIENTS AND METHODS: Patients naïve to ophthalmic surgery were randomized to subconjunctival injection of either a 0.5 mL cefazolin-balanced salt solution (0.3 mL cefazolin and 0.2 mL balanced salt solution) or 0.5 mL cefazolin-lidocaine solution (0.3 mL cefazolin and 0.2 mL 2% lidocaine) during retinal surgery with a retrobulbar block. Pain scores were obtained at the start of surgery, middle of surgery, before and after cefazolin administration, and postoperatively. RESULTS: A total of 54 patients were recruited; 44.6% were male, and the mean age was 60.1 years ± 13.5 years. There were no statistically significant differences between the groups' operative characteristics or pain scores at each study time point. CONCLUSION: In pars plana vitrectomy with or without phacoemulsification and intraocular lens insertion, subconjunctival cefazolin mixed with lidocaine conferred no added analgesic benefit. [ Ophthalmic Surg Lasers Imaging Retina . 2017;48:881–886.]

Primary sclerosing cholangitis (PSC) often coexists with inflammatory bowel disease (IBD) and can be complicated by cholangiocarcinoma (CCA), a lethal malignancy for which reliable predictors remain unknown. We aimed to characterize the influence of colectomy and IBD duration on risk of CCA in patients with PSC-IBD.A retrospective review of patients with PSC-IBD seen at the Mayo Clinic, Rochester, between January 2005 and May 2013 was performed. The primary outcome was time to development of CCA and our goal was to determine whether the risk differed between patients with and without colectomy. Risk factors were assessed using univariable and multivariable Cox proportional hazard models where colectomy, IBD disease duration, and development of advanced liver disease were treated as time-dependent covariates.A total of 399 patients with PSC-IBD were included in the study, of whom 137 had a colectomy and 123 patients developed CCA. Age-adjusted univariate Cox proportional hazard models demonstrated that colectomy (hazard ratio (HR) 1.53, 95% confidence interval (CI) 1.05-2.22, P=0.02) and duration of IBD (HR 1.37, 95% CI 1.15-1.63, P0.01) were associated with an increased risk of CCA, and colonic neoplasia (HR 1.52, 95% CI 0.97-2.37, P=0.06) and colectomy for colonic neoplasia (HR 1.62, 95% CI 1.01-2.61, P=0.05) approached significance. Among patients with a history of colectomy, colonic neoplasia as the indication for surgery was associated with a particularly increased risk of CCA (HR 2.91, 95% CI 1.24-6.84, P=0.01) compared with medically refractory disease. On multivariate analysis, duration of IBD remained significantly associated with CCA (HR 1.33, 95% CI 1.11-1.60, P0.01). The influence of IBD duration on CCA risk was not modified after colectomy (P=0.69).Prolonged duration of IBD is associated with an increased risk of CCA in patients with PSC-IBD, and colectomy itself does not modify this risk. These findings identify a subset of patients who are at high risk of this lethal complication and in need of close surveillance.

Strategies to improve donor heart utilization are required in the setting of limited donor availability. One innovative strategy is to consider the use of hepatitis C viremic (HCV) nucleic acid amplification test positive donors in hepatitis C-negative recipients, given the availability of highly effective direct acting antiviral agents. We utilized United Network for Organ Sharing data to evaluate the geographic distribution, clinical characteristics, and post-transplant outcomes of HCV+ donor hearts.The United Network for Organ Sharing registry was queried for all HCV+ recovered donors and those considered for heart donation classified by sex, age group, United Network for Organ Sharing region, and cause of death from January 1, 2014, to December 31, 2017. Propensity score matching (3:1) was applied to the recipients based on the index for mortality prediction after cardiac transplantation score and donor risk index. A total of 1306 HCV+ donors were recovered from 2014 to 2017 of whom 1078 (82.5%) were 18 to 49 and predominantly from the Appalachia region (United Network for Organ Sharing regions 2, 3, and 11). A total of 64 (5%) HCV+ donor hearts were transplanted in this interval. The match-adjusted risk difference in survival was estimated to be 0.87% ( P=0.83) at 12 months.To meet the demands of heart transplantation, we must consider additional strategies to expand the donor pool. From 2014 to 2017, despite availability of highly effective direct acting antiviral therapy, only 5% of HCV+ donor hearts were accepted for transplantation. National efforts may be required to capitalize on this resource while we continue to carefully monitor the safety of this novel approach.

PURPOSE Cardiac resynchronization therapy (CRT) has emerged as a beneficial therapy for heart failure (HF) patients. It has been shown to enhance cardiac pump function and increase exercise capacity in patients with HF who display wide QRS complex on their electrocardiogram. To date, few studies have assessed daily physical activity (PA) in CRT patients. The objective of this pilot study was to assess the impact of CRT on the physical function and daily PA of HF patients who met the standard indications for CRT implantation. METHODS The daily PA of 18 CRT patients was measured using a SenseWear Armband for ∼3 d. Daily PA measurements included steps/d and time spent sedentary (≤1.5 metabolic equivalent tasks), in light PA (1.6-2.9 metabolic equivalent tasks), and in moderate-vigorous PA (≥3 metabolic equivalent tasks). To assess exercise capacity, a 6-min walk test was performed pre- and post-CRT. RESULTS There was no significant change in the 6-min walk test distance from pre- to post-CRT (383 ± 99 m at baseline vs 402 ± 104 m post-CRT). There was a decrease in total steps/d from 3405 ± 2334 pre-CRT to 2553 ± 1692 post-CRT (P = .017). Furthermore, no significant changes were observed pre- to post-CRT with regard to the additional PA assessments. CONCLUSIONS Our patients exhibited a sedentary lifestyle pre- and post-CRT. These findings underscore the need for a cardiac rehabilitation program that encourages post-CRT patients to decrease sedentary time.

Importance The transscleral XEN Glaucoma Gel Microstent (XEN‐GGM, Allergan Plc., Parsippany, New Jersey) is implanted by a minimally invasive ab interno technique. Background The present study aims to assess the long‐term clinical outcomes in patients after XEN‐GGM implantation. Design This prospective, non‐randomized, multi‐centred study was conducted in three countries (Austria, Canada and Germany). Participants Sixty‐four consecutive eyes of 64 patients with open angle glaucoma received the XEN‐GGM (63 μm) without Mitomycin C. Thirty‐five (55%) were solo procedures, and 29 (45%) were combined with cataract surgery. Methods Visits were planned at baseline, 6 months, 1, 2, 3 and 4 years postoperatively. Main Outcome Measures The main outcome measures were mean intraocular pressure (IOP), mean number of IOP lowering medication. Secondary outcome parameters were: visual acuity, visual fields and complete surgical failure (defined as presence of a secondary IOP lowering procedure or loss of light perception) at 4 years, postoperatively. Results Mean best‐medicated baseline IOP was 22.5 ± 4.2 mmHg and decreased significantly to 13.4 ± 3.1 mmHg 4 years postoperatively (−40%, n = 34, P < 0.001). Mean number of IOP lowering medication decreased significantly from 2.4 ± 1.3 preoperatively to 1.2 ± 1.3 (−50%, n = 34, P < 0.001) postoperatively. Visual field mean deviation showed no significant change between preoperative and postoperative examinations. Complete surgical failure rate per year was 10%. Conclusions and Relevance The XEN‐GGM resulted in lower IOP and a reduction in medications from baseline over 4 years of follow‐up. There was no detectable decrease in visual fields over the study. The surgical failure rate is comparable to other filtration surgeries.

To evaluate postoperative interventions, visual outcomes, and number of postoperative office visits after standalone ab interno gelatin microstent implantation with mitomycin C (MMC) vs. trabeculectomy with MMC.International, multicenter, retrospective cohort study.A total of 354 eyes of 293 patients, including 185 microstent eyes and 169 trabeculectomy eyes.Consecutive eyes with uncontrolled glaucoma underwent microstent or trabeculectomy surgery from January 1, 2011, through July 31, 2015, at 4 academic ophthalmology centers: Toronto, Canada; Frankfurt, Germany; Salzburg, Austria; and Leuven, Belgium.Assessed outcomes included (1) in-clinic interventions, (2) transconjunctival needle revision (TCNR), (3) postoperative visits at 1 and 3 months, (4)2 lines vision loss at last follow-up, (5) complete visual recovery, and (6)0.5 or1 diopter (D) of surgically induced astigmatism.Ninety-five (51.4%) of the microstent eyes and 105 (62.1%) of the trabeculectomy eyes underwent an intervention by last follow-up (log-rank P = 0.0004). The most common intervention was TCNR, followed by laser suture lysis. Seventy-eight (42.2%) microstent eyes and 55 (32.5%) trabeculectomy eyes received TCNR (adjusted hazard ratio [HR], 1.73 [95% confidence interval (CI), 1.10-2.71]): 128 total TCNRs in the microstent group and 95 in the trabeculectomy group. Predictors for TCNR included prior laser peripheral iridotomy and diabetes. Microstent eyes had on average 1.00 (standard deviation 2.32) fewer visits compared with trabeculectomy eyes in the first month (P0.001), adjusted for baseline characteristics. The percentage of eyes that had lost2 lines of vision at last follow-up or reoperation was 12.4% (95% CI, 8.0%-18.7%) and was 21.9% (95% CI, 15.3%-30.1%) adjusted (P = 0.0383). A higher proportion of microstent eyes regained their baseline preoperative visual acuity compared with trabeculectomy eyes (log-rank P = 0.0250; adjusted HR, 1.46 [95% CI, 1.10-2.00]). Altogether, 25.3% (95% CI, 15.3%-38.9%) of microstent eyes and 40.7% (95% CI, 27.7%-55.3%) of trabeculectomy eyes had0.5 D surgically induced astigmatism on an adjusted basis; 8.0% (95% CI, 3.2%-18.6%) vs. 17.3% (95% CI, 8.9%-9.8%) had1 D.Microstent eyes had more TCNRs (though fewer in-clinic interventions), fewer postoperative visits, and less vision loss, and experienced less surgically induced astigmatism, than trabeculectomy eyes. Overall, the postoperative course was less intensive for the microstent, except for more TCNRs.

BACKGROUND & AIMS Primary biliary cirrhosis (PBC) is characterized by chronic cholestasis and disease-specific antimitochondrial antibodies (AMA). A high prevalence of AMAs in first-degree relatives (FDRs) of PBC probands has been reported, although the natural history of such patients has not been described. We aimed to assess the risk of developing PBC in AMA+ FDRs of patients with PBC. METHODS First-degree relatives recruited to the Mayo Clinic PBC Genetic Epidemiology Registry and Biorepository were followed for disease onset after recruitment. Development of PBC was ascertained via self-report during a telephone interview and/or via proband report on a questionnaire. Chi-squared test and t-test were used to assess the differences between categorical and continuous variables respectively. A mixed-effects model was used to assess the change in biochemical profiles over time. RESULTS Forty AMA+ and 423 AMA- subjects were included and followed for a median of 8.9 and 8.4 years respectively. Overall, 3% (n = 15) of FDRs were diagnosed with PBC, and AMA+ FDRs had a higher risk than AMA- FDRs (24% vs. 0.7%, P < 0.01). However, among undiagnosed FDRs, only 4% of AMA+ (n = 1) and 0.4% of AMA- (n = 1) FDRs were diagnosed with PBC (P = 0.17) during the follow-up period. None of the AMA+ FDRs with normal alkaline phosphatase at baseline developed PBC in follow-up. CONCLUSIONS Our results suggest a low risk of developing PBC over time in FDRs of patients with PBC, particularly those without biochemical evidence of cholestasis at baseline. These data are useful in counselling and reassuring relatives of their overall favourable prognosis.

Learning Objectives After completing this course, the reader will be able to: Characterize and compare the clinical behavior and outcome of patients with epithelioid sarcoma and unclassified sarcoma with epithelioid features.Identify differentiation and other tumor-related molecular markers in human ES and USEF specimens described in this study. This article is available for continuing medical education credit at CME.TheOncologist.com Background. Epithelioid sarcoma (ES) and unclassified sarcoma with epithelioid features (USEF) are clinically and therapeutically unresolved. We compared ES and USEF patients' clinical behavior, treatment, outcome, and molecular marker expression. Furthermore, preclinical ES study models were developed to enable comprehensive benchside investigations. Patients and Methods. A database of ES and USEF patients (n = 116) treated since 1992 was created. A clinically annotated ES–USEF tissue microarray (TMA) was assayed for tumor-related markers. Newly established human and commercially available ES cell lines were characterized and tested in vivo. Results. ES and USEF patients presenting with localized disease exhibited 22% and 25% local recurrence rates, 35% and 19% nodal metastasis rates, and 41% and 53% distant metastasis rates (median follow-up, 54 months and 39 months, respectively). The 5- and 10-year disease-specific survival rates were 88% and 43% and 52% and 42% (ES and USEF, respectively). TMA immunohistochemistry identified integrase interactor (INI)-1 loss, cancer antigen 125, and p53 nuclear expression as significantly more common in ES than USEF cases. Both cell lines preserved ES morphological and biochemical characteristics in vitro and in vivo; loss of INI-1 was shown to occur in both lines. Conclusions. Enhanced knowledge of ES and USEF clinical behavior, marker expression, and molecular determinants, extended via experimental models, will hopefully accelerate development of urgently needed effective targeted therapies for ES and USEF.

KLONIS, D., et al.: Automatic Sensor Algorithms Expedite Pacemaker Follow-ups.Objective: Automatic algorithms can be used to optimize settings and reduce the duration of pacemaker (PM) clinical follow-up. Methods: This study prospectively evaluated 87 patients (74.2 ± 10.7years old, 52% men) who received PM with the Autoslope algorithm. Patients randomized to the manual group (group M,n = 43) performed a walk test and used sensor-indicated rate histograms to adjust the sensor, while in the automatic group (group A,n = 44) the sensor was automatically adjusted by the Autoslope. The patients were followed for 6 months. Follow-up time required for device interrogation and optimal sensor set-up, and the number of sensor parameters reprogramming were recorded. Changes in the patients' activity level were also evaluated. Results: Group A required significantly less follow-up time than group M (9.4 ± 5.7 minvs13.5 ± 8.5 min, P = 0.0002). The average number of sensor parameters reprogrammed during visits was significantly lower in group A than M(0.6 ± 0.9vs0.9 ± 1.3, P = 0.048). Threshold was adjusted 34.4% of the time in the sensor evaluations in group M versus 12.9% in group A (P = 0.0004). Although more patients in group A reported being more active, the changes in patients' activity level did not lead to increasing sensor setup time or number of parameter reprogramming in either group. Conclusions: Auto sensor adjustment required less time during routine PM clinical follow-up by reducing steps needed for manual sensor threshold adjustment.(PACE 2003; 26[Pt. II]:225–228)

Pericarditis has been noted as a potential complication of pacemaker implantation. This study evaluated the risk of developing pericarditis following pacemaker implantation with active-fixation atrial leads. Included were 1,021 consecutive patients (mean age 73.4+/-0.4 years, range 16-101 years; 45.2% women) undergoing new pacemaker system implantation between 1991 and 1999 who were reviewed for the complication of pericarditis. The incidence and outcomes of postimplantation pericarditis in patients receiving active-fixation atrial leads were compared to those not receiving these leads. Of 79 patients who received active-fixation atrial leads, 4 (5%) developed pericarditis postpacemaker implantation. Of 942 patients with passive-fixation atrial leads or no atrial lead (i.e., a ventricular lead only), none developed pericarditis postoperatively (P < 0.001). Of patients receiving active-fixation ventricular leads only (n = 97), none developed pericarditis. No complications were apparent at the time of implantation in patients who developed pericarditis. Pleuritic chest pain developed between 1 and 28 hours postoperatively. Three patients had pericardial rubs without clinical or echocardiographic evidence of tamponade. They were treated conservatively with acetylsalicylic acid or ibuprofen and their symptoms resolved without sequelae in 1-8 days. One patient (without pericardial rub) died due to cardiac tamponade on postoperative day 6. Postmortem examination revealed hemorrhagic pericarditis with no gross evidence of lead perforation. Pericarditis complicates pacemaker implantation in significantly more patients who receive active-fixation atrial leads. It may be precipitated byperforation of the atrial lead screw through the thin atrial wall. Patients developing postoperative pericarditis should befollowed closely due to the risk of cardiac tamponade.

OBJECTIVES This investigation was designed to determine the feasibility and cost-effectiveness of direct discharge from the coronary/intermediate care unit (CICU) in 497 consecutive patients with an acute myocardial infarction (AMI). BACKGROUND Although patients with an AMI are traditionally treated in the CICU followed by a period on the medical ward, the latter phase can likely be incorporated within the CICU. METHODS All patients were considered for direct discharge from the CICU with appropriate patient education. The 6-week postdischarge course was evaluated using a structured questionnaire by a telephone interview. RESULTS There were 497 patients (men = 353; women = 144; age 63.5 ± 0.6 years) in the study, with 29 in-hospital deaths and a further 11 deaths occurring within 6 weeks of discharge. The mode length of CICU stay was 4.0 days (mean 5.1 ± 0.2 days): 1 to 2 (12%), 3 (19%), 4 (21%), 5 (14%), 6 to 7 (19%) and ≥7 (15%) days, respectively with 87.2% discharged home directly. Of the 425 patients surveyed, 119 (28.0%) indicated that they had made unscheduled return visits (URV) to a hospital or physician’s office: 10.6% to an emergency room, 9.4% to a physician’s office and 8.0% readmitted to a hospital. Of these URV, only 14.3% occurred within 48 h of discharge. Compared to historical controls, the present management strategy resulted in a cost savings of Cdn. $4,044.01 per patient. CONCLUSIONS Direct discharge from CICU is a feasible and safe strategy for the majority of patients that results in considerable savings.

Although the incidence of pacemaker-related infection (PMINF) is low, it necessitates removal of the pacing system. There is currently no consensus on antibiotics during implantation.A prospective database on patients undergoing pacemaker surgery from 1991 to 2009 was reviewed to determine factors associated with PMINF. Specifically, three eras of antibiotic use were compared to elucidate the effect of antibiotics on PMINF: no antibiotics, perioperative antibiotics, and peri- plus postoperative antibiotics.There were 3,253 procedures with PMINF identified in 46 (1.4%) patients. Over 19 years, PMINF incidence fell from 3.6% (no antibiotics) to 2.9% (perioperative antibiotics), to 0.4% (peri- plus postoperative antibiotics). On univariate analysis, the following were associated with PMINF: nonuse of postoperative antibiotics (3.0% vs 0.4%, P0.001), year of implant (P0.001), repeat procedures (2.3% vs 1%, P = 0.006), nonuse of perioperative antibiotics (3.6% vs 1.3%, P = 0.027). With postoperative antibiotics, rates were significantly reduced in new implants (1/1,289 = 0.1% vs 22/967 = 2.3%, P0.001) and repeat procedures (7/692 = 1.0% vs 16/305 = 5.2%, P0.001). On multivariate analysis, the following were significant (standardized coefficients denote relative importance): postoperative antibiotics (0.776), repeat procedures (0.508), year of implant (0.142), perioperative antibiotics (0.088).The PMINF rate is reduced significantly by perioperative antibiotics with a further significant reduction with postoperative antibiotics. However, the reduction in PMINF rate could be a result of changes in practice in the different time eras. This study suggests consideration of perioperative followed by postoperative antibiotics to minimize pacemaker infections.

Background Asymptomatic deep vein thrombosis (DVT) occurs in up to 11% of medical inpatients. The incidence of asymptomatic DVT among patients with inflammatory bowel disease (IBD) is unknown but may be even higher. D-dimer is effective for DVT screening, but its utility has not been studied in the IBD population. Methods Hospitalized and ambulatory patients with IBD during flares were recruited between 2009 and 2011. Those with clinical symptoms of venous thromboembolism or previous venous thromboembolism were excluded. We determined the prevalence of DVT among asymptomatic subjects using lower extremity Doppler ultrasound and assessed the performance characteristics of the D-dimer in this high-risk study population. Results We enrolled 101 hospitalized and 49 ambulatory patients with IBD during active flares. There were no cases of proximal DVT detected by lower extremity Doppler ultrasound. The 95% confidence interval (CI) for the rate of proximal DVT was 0% to 2%. D-dimer was elevated in 60% of subjects without DVT, occurring more frequently among hospitalized than ambulatory subjects [89% versus 65%, P = 0.01; adjusted odds ratio (aOR), 4.16, 95% CI, 1.58-10.9]. Other predictors of elevated D-dimer were incremental decade in age (aOR, 1.97; 95% CI, 1.24-3.14); ulcerative colitis versus Crohn's disease diagnosis (aOR, 3.38; 95% CI, 1.29-8.84); and every 10-unit increase in C-reactive protein (aOR, 1.33; 95% CI, 1.09-1.62). Conclusion From this pilot study, there appears to be low prevalence of asymptomatic DVTs among patients with IBD during flares. The high prevalence of elevated D-dimer in DVT-negative patients limits its utility in IBD.

Androgen deprivation therapy in 80 men was associated with declines in bone mineral density (BMD), which were greatest in the first year, and in the lumbar spine compared to controls. Vitamin D use was associated with improved BMD in the lumbar spine and in the first year.Decreased BMD is a common side effect of androgen deprivation therapy (ADT), leading to increased risk of fractures. Although loss of BMD appears to be greatest within the first year of starting ADT, there are few long-term studies of change in BMD, and risk factors for bone loss are not well-characterized.Men aged 50+ with nonmetastatic prostate cancer starting continuous ADT were enrolled in a prospective longitudinal study. BMD was determined by dual-energy x-ray absorptiometry at baseline and yearly for 3 years. Matched controls were men with prostate cancer not receiving ADT. Multivariable regression analysis examined predictors of BMD loss.Eighty ADT users and 80 controls were enrolled (mean age 69 years); 52.5 % had osteopenia and 8.1 % had osteoporosis at baseline. After 1 year, in adjusted models, ADT was associated with significant losses in lumbar spine BMD compared to controls (-2.57 %, p = 0.006), with a trend towards greater declines at the total hip (p = 0.09). BMD changes in years 2 and 3 were much smaller and not statistically different from controls. Use of vitamin D but not calcium was associated with improved BMD in the lumbar spine in year 1 (+6.19 %, p 0.001) with smaller nonsignificant increases at other sites (+0.86 % femoral neck, +0.86 % total hip, p 0.10) primarily in the first year.Loss of BMD associated with ADT is greatest at the lumbar spine and in the first year. Vitamin D but not calcium may be protective particularly in the first year of ADT use.

To better understand the mechanisms contributing to improved exercise capacity with cardiac resynchronization therapy (CRT), we studied the effects of 6 mo of CRT on pulmonary O(2) uptake (Vo(2)) kinetics, exercise left ventricular (LV) function, and peak Vo(2) in 12 subjects (age: 56 ± 15 yr, peak Vo(2): 12.9 ± 3.2 ml·kg(-1)·min(-1), ejection fraction: 18 ± 3%) with heart failure. We hypothesized that CRT would speed Vo(2) kinetics due to an increase in stroke volume secondary to a reduction in LV end-systolic volume (ESV) and that the increase in peak Vo(2) would be related to an increase in cardiac output reserve. We found that Vo(2) kinetics were faster during the transition to moderate-intensity exercise after CRT (pre-CRT: 69 ± 21 s vs. post-CRT: 54 ± 17 s, P0.05). During moderate-intensity exercise, LV ESV reserve (exercise - resting) increased 9 ± 7 ml (vs. a 3 ± 9-ml decrease pre-CRT, P0.05), and steady-state stroke volume increased (pre-CRT: 42 ± 8 ml vs. post-CRT: 61 ± 12 ml, P0.05). LV end-diastolic volume did not change from rest to steady-state exercise post-CRT (P0.05). CRT improved heart rate, measured as a lower resting and steady-state exercise heart rate and as faster heart rate kinetics after CRT (pre-CRT: 89 ± 12 s vs. post-CRT: 69 ± 21 s, P0.05). For peak exercise, cardiac output reserve increased significantly post-CRT and was 22% higher at peak exercise post-CRT (both P0.05). The increase in cardiac output was due to both a significant increase in peak and reserve stroke volume and to a nonsignificant increase in heart rate reserve. Similar patterns in LV volumes as moderate-intensity exercise were observed at peak exercise. Cardiac output reserve was related to peak Vo(2) (r = 0.48, P0.05). These findings demonstrate the chronic CRT-mediated cardiac factors that contribute, in part, to the speeding in Vo(2) kinetics and increase in peak Vo(2) in clinically stable heart failure patients.

Transcatheter ablation of nodal tissue is used for the treatment of arrhythmia resistant to medical therapy. We have investigated the use of laser induced fluorescence spectroscopy for the in vitro recognition of nodal conduction tissue. Twelve fresh human necropsy specimens (48 hours) were obtained from sinoatrial node and atrioventricular node areas. Spectra were recorded during excitation at 308 nm (XeCl excimer laser, 1.5-2.0 mJ/pulse, 10 Hz). Ech area examined was marked for subsequent histologic examination. Four hundred eleven spectra were obtained, of which 37 contained nodal conduction tissue (21 sinoatrial, 16 atrioventricular node). Normalized fluorescence emission intensity from these areas was compared with that of surrounding endomyocardial tissue at 18 wavelengths and 35 ratios of fluorescence intensity at selected wavelengths. Spectra recorded from nodal tissue could be clearly distinguished by a visible decrease in fluorescence emission intensity at wavelengths from 440 to 500 nm (P0.0006 at 450 nm), peak area, and peak width when compared to that of adjacent atrial endomyocardial tissue. Nodal conduction tissue was also distinguished from ventricular endocardium (14 spectra) by an increase in fluorescence emission at 430 to 550 nm (P0.0001). The specificity was 73% and 88% and the sensitivity was 73% and 60% for sinus nodal and atrioventricular nodal conduction tissue identification, respectively. A ratio of fluorescence emission intensity1.3 for 380/475 nm was able to detect nodal conduction tissue (P0.001).Laser induced fluorescence can differentiate nodal conduction tissue from atrial and ventricular endocardium and may provide a new diagnostic tool for the recognition and subsequent ablation of nodal conduction tissue.

Atrioventricular synchronous pacing offers advantages over fixed-rate ventricular (VVI) pacing both at rest and during exercise. This study compared the hemodynamic effects at rest and exercise of ventricular pacing at a rate of 70 beats/min, ventricular pacing where the rate was increased during exercise and dual chamber pacing. Ten patients, age 63 +/- 8 years, with multiprogrammable DDD pacemakers were studied using supine bicycle radionuclide ventriculography. Radionuclide data during dual chamber pacing was acquired at rest and during a submaximal workload of 200-400 kpm/min. The pacemakers were then programmed to VVI pacing at a rate of 70 beats/min, and 1 week later, studies were repeated in the VVI mode at rest, during exercise at a rate of 70 beats/min, and during exercise with the VVI pacemaker programmed to a rate adapted to the DDD pacing exercise rate. At rest, the cardiac output was lower in the VVI compared with the AV sequential mode (4.1 +/- 1.1 vs 5.7 +/- 1.1 1/min, P less than 0.01). During exercise, the cardiac output increased from resting values in the DDD and VVI pacing modes, however cardiac output in the rate-adapted VVI mode was higher than in the VVI mode with the rate maintained at 70 beats/min (8.1 +/- 1.5 vs 6.3 +/- 1.1 1/min, P = 0.02). Three patients completed lower workloads with VVI pacing at 70 beats/min compared with AV synchronous pacing. At rest, AV sequential pacing was superior to VVI pacing, suggesting the importance of the atrial contribution to ventricular filling. With VVI pacing during exercise, cardiac output was improved with an increased pacemaker rate, suggesting that the heart rate response during exercise was the major determinant of the higher cardiac output.

Numerous trials have demonstrated survival benefits using implantable cardioverter defibrillators (ICDs) for primary prevention in selected patients with left ventricular (LV) systolic dysfunction. However, eligibility criteria differed across these trials. Without a risk stratification scheme that clearly identifies those who will benefit, there remains debate about which patients with heart failure (HF) should receive ICDs for primary prevention. To explore the implications of applying different eligibility criteria, this study evaluated all patients seen in a specialized HF clinic from August 2003 to January 2004. Of the 309 consecutive patients in the cohort, 46 were excluded because their HF complicated recent myocardial infarcts (n = 3); their LV ejection fractions were not measured (n = 9); or their HF was due to valvular disease, myocarditis, or peripartum cardiomyopathy (n = 34). The Multicenter Automatic Defibrillator Implantation Trial-II criteria were met by 85 patients (32%), and 134 patients (51%) met the Sudden Cardiac Death in Heart Failure Trial criteria. Even allocation decisions based on randomized trial evidence can have vastly different resource implications depending on which trial is chosen. Thus, the development and validation of a risk stratification scheme to identify those patients most likely to benefit from ICDs for primary prophylaxis should be a research priority.

Atrial-based cardiac pacing modalities were chosen in 341 of 684 (50%) patients selected for permanent cardiac pacing at the Grey Nuns Community Health Center between 1989 and 1995. There were 183 males and 158 females. Mean age was 70 years (range 8-97 years). The indications for atrial-based pacing were: advanced atrioventricular (AV) block (n = 166) 49%; sick sinus syndrome (n = 153) 45%; hypersensitive carotid sinus syndrome (n = 11) 3%; neurocardiac syncope (n = 10) 2.9%; and hypertrophic cardiomyopathy (n = 1) 0.3%. Forty-eight patients had a known history of paroxysmal atrial arrhythmias. All patients had routine follow-up performed at 24 hours, 7 days, 6 weeks, 3 months, and then 6 biannually. Mean follow-up was 6.5 years (range 1 month to 12 years). Observed survival of the programmed atrial-based modality was compared to the original mode chosen at the time of implantation. Thirty-five of 37 (95%) chosen for AAIR modes remain programmed AAIR. Twenty-two of 24 (92%) chosen for VDDR modes remain programmed VDDR. Two hundred and fifty-five of 280 (91%) chosen for DDD or DDDR modes remain programmed DDDR. Two of 37 (5%) patients originally implanted with AAI pacing systems were upgraded to DDDR mode due to new onset AV block. One of 24 (4%) patients originally implanted with a VDDR pacing system was upgraded to DDDR due to loss of atrial sensing of the single pass lead. Twenty-six of 304 (8.5%) patients originally implanted with DDD/DDDR (n = 25) and VDDR (n = 1) pacing systems were reprogrammed to VVI or VVIR: 16 (62%) due to sustained refractory atrial arrhythmias; 5 (19%) due to atrial lead malfunction; and 5 (19%) due to reasons unrelated to the pacing system. With careful review of the patients' conduction disorder and appropriate selection of pacing modality, the observed survival of long-term atrial-based pacing remains at 92% when compared to the chosen modality at the time of implantation. Atrial-based pacing may be used to reduce the incidence of atrial dysrhythmia with careful programming of the base atrial pacing rates.

Background: The DANPACE study suggested implanting dual-pacing dual-sensing dual-response rate-adaptive (DDDR) pacemakers in patients with sick sinus syndrome, even though 90.7% of their atrial-pacing atrial-sensing inhibited-response rate-adaptive (AAIR) group did not require upgrade. Most centers implant DDDR pacemakers due to risk of future atrioventricular (AV) block. Given that AAIR pacemakers are less expensive, have one less lead with potentially one less point of complication, we question whether DDDR pacemakers are superior to AAIR pacemakers. We aim to describe long-term outcomes of AAIR implants. Methods: Patients presenting to the Grey Nuns Hospital in Edmonton, Canada from 1990 to 2012 with sick sinus syndrome without AV block had AAIR pacemakers implanted. Outcomes that were measured over the follow-up time included need for ventricular lead reoperation, incidence of AV block and incidence of sudden cardiac death from AV block. Results: During this period, 330 patients presented with sick sinus syndrome. Eighty-seven (26.4%) patients met criteria for and received AAIR pacemakers. Seventy-eight (91.8%) did not require upgrade over mean follow-up of 10.6 ± 0.6 years. Amongst this group, 31 patients (39.7%) were alive, whereas 47 (60.3%) were deceased at end of follow-up due to other comorbidities. No sudden deaths were attributable to AV block. Only 7 patients (8.2%) required ventricular lead reoperation: 2 (2.4%) presented urgently with symptomatic AV block; 3 (3.5%) had atrial fibrillation requiring beta-blockade; 1 (1.2%) had atrial lead dislodgment; and 1 (1.2%) was electively upgraded at battery end-of-life. Conclusions: This study looks at safety of AAIR pacemakers with only 2.4% of patients developing AV block requiring urgent upgrade. Approximately 91.8% of patients remained with their original AAIR pacemakers (mean follow-up 10.6 vs 5.4 years in DANPACE). Our findings are similar to the DANPACE study but our conclusions are different as we believe AAIR pacing should be considered for selected patients with sick sinus syndrome without AV block.

OBJECTIVES To assess the feasibility and safety of exercise testing (ET) using a Bruce protocol (BPR) within three days of an acute myocardial infarction (AMI) with the data obtained from a prospectively managed database. BACKGROUND Exercise testing after AMI is usually done between days 4 and 6 and often using a “low-level” protocol. Earlier testing with BPR may allow for efficient triage. METHODS Patients were considered for early ET when off intravenous nitroglycerine with no rest angina, uncontrolled cardiac failure or arrhythmias. RESULTS Of 300 consecutive AMI patients who underwent an ET, 216 (72.0%; M = 163, F = 53; age mean 59 ± 0.8 SEM, range 34 to 83 years) had ET within three days of admission. There were 124 (57%) negative, 56 (26%) positive and 36 (17%) indeterminate tests. The maximum heart rate achieved was 116 ± 1 beats/min (range 64 to 163), which was 72.2 ± 0.8% of predicted maximum (86.6% on beta-adrenergic blocking agents at ET; exercise duration = 6.7 ± 0.2 min). Reasons for termination: maximum effort—89 (41%); low-level test target (stage III/IV of BPR)—63 (29%); positive ST segment change—19 (9%); severe chest pain—12 (5.5%); reaching 90% predicted maximum heart rate—6 (3%); nonsustained ventricular tachycardia—1 (0.5%); other—26 (12%). Fourteen (6.5%) patients had minor complications (i.e., drop in systolic pressure, chest pain >5 min) with no cardiac arrests, AMIs or deaths. After the ET, 87 (40%) patients were discharged the same day, 73 (34%) the next day. CONCLUSIONS The majority of ETs after an AMI can be done using the Bruce protocol within three days of admission with a very low incidence of complications. This can lead to early triage and potential cost savings.

Background Tachyarrhythmias can cause substantial morbidity and mortality in infants and very young children. Our objective was to assess early and late outcomes in children undergoing radiofrequency catheter ablation before their second birthday. Methods This is a retrospective review of medical records from 1995 till 2009 at a single institution with a large referral base. Results Thirty-four children younger than 2 years of age were brought to the electrophysiology laboratory for catheter ablation for tachyarrhythmia. Radiofrequency ablation (42 procedures) was performed in 31 children (mean weight, 7.4 kg; range, 2.6-12.3 kg). Tachyarrhythmias were atrioventricular re-entry tachycardia (19), ectopic or multifocal atrial tachycardia (6), atrial flutter (1), ventricular tachycardia (3), and congenital junctional ectopic tachycardia (2). Seventeen children presented with tachycardia-induced cardiomyopathy and heart failure. Three patients required extracorporeal life support prior to the procedure. Radiofrequency catheter ablation was successful in 74% of these very young children vs 91% in a comparison group of children older than 2 years (n = 447). Among patients with initially successful ablations, there was no tachyarrhythmia recurrence during medium- to long-term follow-up (1.4-15.0 years; mean, 7.3 years). Major complications occurred in 4 very young children. Eight of 11 patients in whom ablation failed or could not be done required another form of continued aggressive treatment. Conclusion Catheter ablation is indicated and successful in critically ill infants with life-threatening tachyarrhythmia refractory to medical therapy. Initially successful procedures are associated with excellent long-term outcomes, but significant complication rates require that such procedures be reserved for carefully selected patients and performed by highly skilled staff.

We assessed the value of clinical electrophysiologic study using intracardiac recording and programed electrical stimulation in 34 patients who had unexplained syncope and/or presyncope. All patients had normal electrocardiograms, and no abnormality was detected by clinical examination, ambulatory electrocardiographic recording, or treadmill testing. The electrophysiologic results were diagnostic in four patients (11.8 percent) and led to appropriate therapy that totally relieved symptoms. The results were abnormal but not diagnostic in two patients (5.8 percent) and normal in the remaining 28 patients (82.4 percent). The patients were followed for a mean period of 15 months (range two to 44) after electrophysiologic testing. Sixteen patients (47 percent) had no further episodes in the absence of any intervention. In four patients (11.8 percent), a definitive diagnosis was made during follow-up. In seven patients, permanent pacing was instituted empirically with relief of syncope. Two patients continued to have syncopal spells. We conclude that the diagnostic yield of electrophysiologic testing is low in a patient population that has no electrocardiographic abnormality or clinical evidence of cardiac disease. Empirical permanent pacing in patients with symptoms continuing after our study appeared to be beneficial, but this result is difficult to evaluate because of the high incidence of spontaneous remission in this group. Persistent attempts to document electrocardiographic abnormalities during a typical episode of symptoms appears to be the only definitive way to confirm or exclude an arrhythmic cause of the symptoms.

Intermittent loss of the delta wave in the Wolff-Parkinson-White (WPW) syndrome may result from precarious conduction over the accessory pathway and, as such, would predict a benign prognosis in the event of the occurrence of atrial fibrillation (AF). We evaluated 52 consecutive patients referred for the assessment of the WPW syndrome and determined the prevalence of intermittent preexcitation using review of serial electrocardiograms, ambulatory monitoring, and treadmill testing. All patients subsequently had electrophysiologic testing using standard techniques to determine the properties of the accessory pathway. Of the 52 patients, 26 (50%) were found to have intermittent preexcitation as defined by loss of the delta wave with concomitant prolongation of the P-R interval on at least 1 occasion. These patients had longer effective refractory periods of the accessory pathway (356 +/- 114 versus 295 +/- 29 ms, mean +/- standard deviation, p less than 0.05) and longer shortest cycle lengths maintaining 1:1 anterograde conduction (426 +/- 171 versus 291 +/- 63 ms, p less than 0.02) than their counterparts with constant preexcitation. During AF, 15% of patients with intermittent preexcitation had shortest R-R intervals between preexcited beats less than 250 ms, versus 50% of patients with constant preexcitation (p less than 0.01). These data support the hypothesis that intermittent preexcitation suggests a benign prognosis in the event of AF. A careful search for intermittent preexcitation may yield important prognostic information in asymptomatic subjects and obviate further investigation.

The electrophysiologic effects of intravenous verapamil (a bolus dose of 0.15 mg/kg body weight followed by infusion of 0.005 mg/kg per min) were compared with those of oral verapamil (80 mg every 6 hours for 48 hours) in eight patients who had paroxysmal supraventricular tachycardia. The mechanism of tachycardia was atrioventricular (A-V) nodal reentry in four patients and A-V reentry utilizing an accessory pathway for retrograde conduction in the remaining four. The electrophysiologic effects of oral and intravenous verapamil were similar. Both preparations significantly prolonged anterograde effective and functional refractory periods of the A-V node (p less than 0.001). Both significantly increased the shortest pacing cycle length maintaining 1:1 anterograde conduction over the A-V node (p less than 0.001). Retrograde conduction over the A-V node was greatly prolonged with verapamil in one patient but was unaffected in the others. There was no significant effect on sinoatrial conduction time, sinus nodal recovery time or atrial or ventricular refractoriness. Both preparations prevented induction of tachycardia in six patients none of whom had recurrence of sustained tachycardia while receiving long-term oral therapy (5 to 10 months). Neither preparation had a significant effect in two patients and this predicted failure of long-term oral therapy in one of these patients. The results of acute drug testing with intravenous verapamil can be extrapolated to predict the electrophysiologic results and response to long-term therapy with oral verapamil.

We determined the effects of single intravenous (10 mg) and oral (80, 160 mg) doses of verapamil in 8 digitalized patients with chronic atrial fibrillation. The time course of drug effect was analyzed with computer assistance by considering several measures in atrial fibrillation, including average R-R interval (ARR), shortest R-R interval (SRR), longest R-R interval (LRR), and variability of R-R intervals. Peak plasma concentrations of verapamil were observed immediately after intravenous verapamil (mean elimination half-life of 3.3 h) and 1 hour after oral verapamil (mean elimination half-life 3.4 h, 80 mg; 3.1 h, 160 mg). In contrast to previous studies, we observed the maximum bradycardic effect of intravenous verapamil to occur at one-half to 1 h, and this effect lasted for 2-4 h. Following oral verapamil the peak effect occurred at 3-4 h and lasted for 5-8 h. Analysis of the time course of changes in APR, SRR, LRR, and variability of R-R revealed two distinct "patterns" of ventricular response. In one group (4 of 8 patients), verapamil caused an increase in SRR but a decrease in LRR. R-R intervals "regularized" in this group. In the remaining patients, verapamil increased the SRR but did not change or increase the LRR. This enhanced the observed increase in ARR intervals. We postulate that the decrease in LRR intervals after verapamil is due to reflex adrenergic discharge as a result of the vasodilator effect of the drug while the increase in SRR is a direct effect. These two opposing effects result in regularization of R-R intervals in many patients. Patients demonstrating an increase in LRR intervals after verapamil may not get reflex adrenergic discharge or may be incapable of responding to the latter due to conduction disease; these patients may experience bradycardic complications after verapamil.

This communication reports the sectioning and subsequent examination of 1-mm freehand razor blade sections of the normal 35-day ferret fetus; pregnancy in the ferret lasts for 42 days. Skeletal and other abnormalities obtained after maternal treatment with teratogens, such as trypan blue, mustine hydrochloride, and sodium salicylate are included for comparison with the normal.

We examined the electrophysiologic effects of verapamil in eight patients with the Wolff-Parkinson-White syndrome. Verapamil shortened the antegrade effective refractory period of the accessory pathway in three patients and abbreviated the shortest cycle length with 1:1 conduction over the accessory pathway in two patients. More significantly, verapamil decreased the shortest RR interval between preexcited ventricular complexes during atrial fibrillation (279 +/- 20 msec vs 236 +/- 18 msec, mean +/- SEM; p less than 0.01). After verapamil, two patients required cardioversion for hemodynamic deterioration after acceleration of the ventricular response during atrial fibrillation. In the four patients with predominantly preexcited ventricular complexes during atrial fibrillation the ventricular rate accelerated after verapamil, whereas in patients with predominantly normal ventricular complexes, the average ventricular rate decreased or did not change after verapamil. Verapamil may result in significant acceleration of ventricular response during atrial fibrillation in the Wolff-Parkinson-White syndrome. The safety of verapamil in individual patients with the Wolff-Parkinson-White syndrome should be established by electrophysiologic testing before its use.

Arrhythmogenic right ventricular dysplasia is a myopathy that affects the right ventricular free wall (RVFW) and gives rise to recurrent reentrant ventricular tachycardia (VT). Because the entire right ventricle is potentially arrhythmogenic, ablating a single site of VT may not eliminate the arrhythmia. We developed an operation to confine any arrhythmic activity arising from the right ventricle to that chamber: total disconnection of the RVFW from the left ventricle. We performed RVFW disconnection in two patients with refractory VT associated with arrhythmogenic right ventricular dysplasia. At least two sites or origin of morphologically distinct VT were identified in the RVFW in each patient. RVFW disconnection was carried out under normothermic cardiopulmonary bypass. An encircling incision was made along the attachment of the RVFW to the aortoventricular unit and the tricuspid annulus; the right coronary artery and its RVFW branches were left intact. Electrical activity of the two chambers became dissociated, and VT arising from the RVFW was confined to that chamber. Postoperatively, there was no clinical evidence of hemodynamic impairment (follow-up 4 months and 3 months). Left ventricular function was unchanged and right ventricular flow was maintained by atrial contraction and motion of the septum toward the RVFW during left ventricular systole. One patient had incessant right ventricular tachycardia confined to the RVFW for 3 weeks. We conclude that RVFW disconnection is feasible and applicable to patients with refractory VT originating in the diffusely diseased RVFW.

We examined the feasibility, effectiveness, and safety of using an intravascular catheter positioned in the right ventricular apex for countershock in a coronary care unit setting in 8 patients who had recurrent ventricular tachyarrhythmia. Countershock using 2.5 to 40 J stored energy (damped sinusoidal wave form) was attempted 115 times to terminate 100 episodes of ventricular tachyarrhythmia (ventricular tachycardia, 91; ventricular flutter, 3; ventricular fibrillation, 6). Eighty-six (87%) of 99 countershock attempts for ventricular tachycardia, 3 (60%) of 5 for ventricular flutter, and 4 (36%) of 11 for ventricular fibrillation were successful using this technique. The catheters remained in stable position for 1 to 16 days without dislodgment. A majority of the countershocks were delivered by the regular nursing staff in the coronary unit. We conclude that low energy countershock through an intravascular catheter system is feasible, safe, and effective in a coronary care unit setting. Such a system should be beneficial in the acute management of patients who have recurrent ventricular tachycardia or fibrillation. The catheter lead may also prove useful in managing ventricular tachyarrhythmias that occur during electrophysiologic studies.

Arrhythmogenic right ventricular dysplasia (ARVD)isa recently described entity characterized byright ventricular myopathic changes andright ventricular tachycardia. Thepresenceor extentofleft ventricular dysfunction inARVD isnotknown. We assessed right ventricular andleft ventricular function andsize insixpatients withARVDbyechocardiography andradionuclide angio- cardiography doneinpatients atrestandduring exercise. Allpatients hadrecurrent ventricular tachycardia ofleft bundle branch blockmorphology, andright ventricular origin oftheventricular tachycardia was confirmed byendocardial mapping infourpatients. Theresults werecompared with those of10normal subjects andfive patients withWolff-Parkinson-White syndrome taking amiodar- one.Thelatter group was a control group,since we didnotwithhold amiodarone therapy infour patients withARVD.Mean(+ SD)right ventricular ejection fraction (EF)inpatients withARVD was 25+ 11%atrestand26 12%during exercise. Innormal subjects right ventricular EFwas 51+ 4% atrestand59 6% during exercise (p .05). Innormal subjects, left ventricular EFwas 61+ 4%atrest and72 5%during exercise (p .05) tothose of normal subjects. We conclude that right ventricular dysfunction predominates inpatients withARVD butlatent left ventricular dysfunction ispresent more often thaniscommonly recognized. These findings may haveimportant diagnostic andtherapeutic implications. Circulation 68,No.2,251-257, 1983.

Intravenous verapamil has been shown to be effective in the acute termination of reentrant supraventricular tachycardia involving the atrioventricular node’ and in slowing the ventricular rate during atrial fibrillation or flutter in patients without preexcitation.‘*2 In patients with the Wolff-Parkinson-White syndrome (WPW), verapamil has been reported to shorten the refractoriness of the accessory pathway,2*3 resulting in an increase in the ventricular response during atria1 fibrillation.2*3 We report a case of ventricular fibrillation immediately following the use of intravenous verapamil in a patient with atria1 fibrillation associated with WPW. The patient was a 13-year-old boy who had been perfectly well until approximately 1 year prior to referral when he started experiencing brief episodes of rapid heart

Many electrocardiographic criteria have been proposed for the differentiation of ventricular extrasystole and supraventricular conduction with aberrancy in atrial fibrillation but the validity of these have not been confirmed by intracardiac studies. We recorded His bundle electrograms in nineteen patients (eleven men, eight women) referred for diagnosis of abnormal QRS complexes in the context of chronic atrial fibrillation. Of 1,068 wide QRS complexes analyzed, 91% proved to be of ventricular origin. Electrocardiographic criteria which were specific for ventricular extrasystole included: left bundle branch block morphology, right bundle branch block morphology with a monophasic R in lead V1 or an RS or QS pattern in lead V6, presence of a "compensatory pause", i.e., compensatory cycle (V2-V3) longer than the average cycle length of ten normally conducted beats preceding the abnormal complex (927 +/- 317 vs 780 +/- 199, mean +/- SD in msec. p less than 0.005), frontal QRS axis of the abnormal complex directed superiorly or to the right and the presence of a "short-long" cycle sequence. Right bundle branch morphology with a triphasic R in lead V1 or QRS pattern in V6 and concordant initial vector in lead V1 or in more than one ECG leads were very specific for supraventricular conduction with aberrancy. Analysis of coupling interval and Ashman's phenomenon, i.e., the long-short cycle sequence, were not specific for supraventricular conduction with aberrancy. We conclude that in digitalis-treated patients with chronic atrial fibrillation the majority of abnormal QRS complexes are of ventricular origin. The diagnosis of ventricular extrasystole or aberrancy can be made using a single ECG lead (V1) and applying a combination of easily applied criteria.

The findings in four patients with marked paradoxical septal motion and an unusual early diastolic sound are presented. Each patient had markedly abnormal right ventricular function. Phonocardiograms, apexcardiograms, and echocardiograms showed the sound to precede the expected timing of a third heart sound and to coincide with the peak leftward displacement of the paradoxically moving septum in early diastole. In two patients the sound was also accompanied by third and fourth heart sounds, revealing a total of five heart sounds on phonocardiographic studies. The sound appeared to originate from the sudden deceleration of the septal mass as it moved leftward during ventricular relaxation.