A glycosylated hemoglobin A1c above 6% (42 mmol/mol) is associated with a high risk of developing Cystic Fibrosis-Related Diabetes and a lower probability of weight gain in both adults and children with Cystic Fibrosis.

OBJECTIVES: The classical glycosylated hemoglobin A1c threshold of 6.5% is an insensitive screening test for cystic fibrosis-related diabetes (CFRD). We sought to identify CF-specific A1C thresholds associated with 1) risk of progression to CFRD and 2) changes in body mass index (BMI) and forced expiratory volume (FEV1). METHODS: We studied the cross sectional and longitudinal associations between A1c, BMI, and FEV1 in 2 cohorts of 223 children (followed for up to 8 years) and 289 adults (followed for a mean of 7.5 ± 4.3 years) with CF but without diabetes at baseline and undergoing regular assessments including Oral Glucose Tolerance Test (OGTT). RESULTS: For the onset of OGTT-defined CFRD optimal A1c threshold was 5.9% in adults (sensitivity: 67% and specificity: 71%) and 5.7% for children (sensitivity: 60% and specificity: 47%). Kaplan-Meier analysis of progression to CFRD according to baseline A1C showed increased the risk of developing CFRD for A1c ≥ 6.0% in adults (P = 0.002) and ≥ 5.5% in children (p = 0.012). Temporal changes in BMI and FEV1 according to baseline A1C in adults were assessed with a linear mixed-effect model, BMI significantly increased over time in subjects with a baseline A1c < 6%, but those with a A1C ≥ 6.0% gained significantly less weight over time (P = 0.05). There was no difference in FEV1 according to baseline A1c category. CONCLUSION: An A1C above 6% may be associated with a high risk of developing CFRD and a lower probability of weight gain in both adults and children with CF.

Glycated Hemoglobin as a First-line Screening Test for Cystic Fibrosis‒Related Diabetes and Impaired Glucose Tolerance in Children With Cystic Fibrosis: A Validation Study.

OBJECTIVES: Our aims in this study were to document the screening rate for cystic fibrosis‒related diabetes (CFRD) in children followed at a cystic fibrosis (CF) clinic in Canada and to evaluate the accuracy of various glycated hemoglobin (A1C) cutoffs to screen for CFRD and impaired glucose tolerance (IGT) in a pediatric CF population. METHODS: The CFRD screening rate was calculated over a follow-up period of up to 8 years among children who attended the CF clinic between 1993 and 2018. Test performance of A1C at various thresholds ranging from 5.5% to 6.2% was compared with the oral glucose tolerance test (OGTT) as the reference method. Children with CF aged ≥10 years with an OGTT performed within 120 days of A1C measurement were included in the analysis. RESULTS: The overall CFRD screening rate was 53.0%. A total of 256 children were included for the A1C performance analysis, of whom 8.6% had an OGTT-confirmed CFRD diagnosis. An A1C threshold of 5.8% demonstrated an optimal balance between sensitivity (90.9%) and specificity (60.7%) for CFRD screening, leading to a potential reduction of 56.3% of the annual required OGTTs. A1C demonstrated poor accuracy for identifying children with IGT. CONCLUSIONS: An A1C threshold ≥5.8% allows for identification of children requiring further CFRD investigations, which may reduce the clinical burden of children with CF without compromising the ability of early CFRD diagnosis.

Influence of pre-diabetic and pancreatic exocrine states on pulmonary and nutritional status in adults with Cystic Fibrosis.

BACKGROUND: In 1992, a landmark study demonstrated clinical deterioration in respiratory function and nutritional status prior to the onset of cystic fibrosis-related diabetes (CFRD). We re-evaluated this outcome. METHODS: The Montreal Cystic Fibrosis Cohort is a prospective CFRD screening study. We performed a 6-year retrospective analysis of nutritional parameters and FEV1 (%) in subjects who developed incident CFRD and in controls who maintained normoglycemia (NG). In the former group, data was collected over 6 years prior to diabetes onset. RESULTS: Subjects (n = 86) had a mean age of 31.7 ± 8.1 years, BMI of 23.0 ± 4.0 kg/m2, and FEV1% of 70.1 ± 24.2%. Eighty-one percent had pancreatic insufficiency (PI). Patients were grouped as follows: NG+PS (pancreatic sufficient) (n = 16), NG+PI (pancreatic insufficient) (n = 21), CFRD+PS (n = 3) and CFRD+PI (n = 46). At their most recent screen NG+PS subjects had significantly greater BMI, as compared to NG+PI and CFRD+PI groups (26.2 ± 3.6 kg/m2 vs 22.6 ± 4.2 kg/m2 vs 22.1 ± 3.5 kg/m2, p = 0.0016). FEV1 was significantly greater in the NG+PS group (91.5 ± 16.8% vs 67.8 ± 25.3% vs 63.5 ± 22.2%, p = 0.0002). The rates of change in weight, BMI, fat mass (%), and FEV1 prior to the most recent visit (NG+PS, NG+PI groups) or to the diagnosis of de novo CFRD were similar between groups. CONCLUSION: In a contemporary context, CFRD onset is not preceded by deterioration in BMI, fat mass, or pulmonary function. Low BMI and FEV1 are more closely associated with PI than a pre-diabetic state.

Thromboembolic Risk After Atriopulmonary, Lateral Tunnel, and Extracardiac Conduit Fontan Surgery.

BACKGROUND: Thromboembolic events contribute greatly to morbidity and mortality following Fontan surgery for univentricular hearts. OBJECTIVES: This study sought to evaluate the effect of type of Fontan surgery on thromboembolic risk. METHODS: A North American multicenter retrospective cohort study enrolled 522 patients with Fontan palliation consisting of an atriopulmonary connection (APC) (21.4%), lateral tunnel (LT) (41.8%), or extracardiac conduit (EC) (36.8%). Thromboembolic complications and new-onset atrial arrhythmia were reviewed and classified by a blinded adjudicating committee. Thromboembolic risk across surgical techniques was assessed by multivariable competing-risk survival regression. RESULTS: Over a median follow-up of 11.6 years, 10- and 20-year freedom from Fontan conversion, transplantation, or death was 94.7% and 78.9%, respectively. New-onset atrial arrhythmias occurred in 4.4, 1.2, and 1.0 cases per 100 person-years with APC, LT, and EC, respectively. APC was associated with a 2.82-fold higher risk of developing atrial arrhythmias (p < 0.001), with no difference between LT and EC (p = 0.95). A total of 71 thromboembolic events, 32 systemic and 39 venous, occurred in 12.8% of subjects, for an overall incidence of 1.1%/year. In multivariable analyses, EC was independently associated with a lower risk of systemic (hazard ratio [HR]: 0.20 vs. LT; 95% confidence interval [CI]: 0.04 to 0.97) and combined (HR: 0.34 vs. LT; 95% CI: 0.13 to 0.91) thromboembolic events. A lower incidence of combined thromboembolic events was also observed with antiplatelet agents (HR: 0.54; 95% CI: 0.32 to 0.92) but not anticoagulation (p = 0.53). CONCLUSIONS: The EC Fontan was independently associated with a lower thromboembolic risk after controlling for time-varying effects of atrial arrhythmias and thromboprophylaxis.

Reducing radiation exposure during procedures performed in the electrophysiology laboratory.

INTRODUCTION: Expert societies recently published strong recommendations to reduce the exposure of patients and staff to ionizing radiation (IR) during interventional and electrophysiology (EP) procedures. However, adherence to these guidelines remains difficult and the impact of implementing such recommendations is poorly characterized. METHODS AND RESULTS: We conducted a single-center cohort study to quantify radiation exposure over time in three EP laboratories at the Montreal Heart Institute during 5,546 consecutive procedures from 2012 to 2015 by 11 primary operators. Overall, 2,618 (47.2%) procedures were catheter-based and 2,928 (52.8%) were device interventions. Interventions to reduce radiation exposure included educational initiatives to raise awareness (i.e., limiting cine acquisition, patient position, table height), slower frame rate, lower radiation dose per pulse, collimation, and integration with 3-D mapping systems and/or MediGuide technology. An 85% reduction in IR exposure was observed from 2012 to 2015, with the mean dose-area-product (DAP) decreasing from 7.65 ± 0.05 Gy·cm2 to 1.15 ± 0.04 Gy·cm2 (P < 0.001). This was true for catheter-based procedures (mean DAP 16.99 ± 0.08 to 2.00 ± 0.06 Gy·cm2 , P < 0.001) and device interventions (mean DAP 4.18 ± 0.06 to 0.64 ± 0.05 Gy·cm2 , P < 0.001). The median effective dose of IR recorded per quarter by 282 cervical dosimeters on EP staff decreased from 0.57 (IQR 0.18, 1.03) mSv in 2012 to 0.00 (IQR 0.00, 0.19) mSv in 2015, P < 0.001. CONCLUSION: Enforcing good clinical practices with simple measures and low-dose fluoroscopy settings are highly effective in reducing IR exposure in the EP lab. These promising results should encourage other EP labs to adopt similar protective measures.

Late Onset Postcapillary Pulmonary Hypertension in Patients With Transposition of the Great Arteries and Mustard or Senning Baffles.

BACKGROUND: There is a paucity of data regarding late-onset pulmonary hypertension (PH) in patients with transposition of the great arteries and atrial switch surgery. METHODS AND RESULTS: A retrospective cohort study was conducted on 140 adults with transposition of the great arteries and atrial switch surgery, age 37.3±7.8, 37.1% female, in order to assess the prevalence and characteristics of late-onset PH and explore associated factors. Patients were followed for a median of 32.3 years after atrial switch surgery and 10.0 years after their first referral visit. PH was detected in 18 of 33 (54.5%) patients who had invasive hemodynamic studies. Average age at diagnosis of PH was 33.9±8.1 years. PH was postcapillary in all, with a mean pulmonary artery pressure of 36±12 mm Hg and mean pulmonary capillary wedge pressure of 28±8 mm Hg. PH was diagnosed in 13 of 17 (76.5%) patients who had cardiac catheterization for heart failure or decreased exercise tolerance. In multivariable analyses, systemic hypertension (odds ratio 9.4, 95% confidence interval 2.2-39.4, P=0.002) and heart failure or New York Heart Association class III or IV symptoms (odds ratio 49.8, 95% confidence interval 8.6-289.0, P<0.001) were independently associated with PH. Patients with PH were more likely to develop cardiovascular comorbidities including atrial (P=0.001) and ventricular (P=0.008) arrhythmias, require hospitalizations for heart failure (P<0.001), and undergo tricuspid valve surgery (P<0.001). Mortality was significantly higher in patients with PH (hazard ratio 9.4, 95% confidence interval 2.1-43.0], P<0.001). CONCLUSIONS: Late-onset postcapillary PH is highly prevalent in adults with transposition of the great arteries and atrial switch surgery and is associated with an adverse prognosis.

Focal Transcatheter Cryoablation: Is a Four-Minute Application Still Required?

INTRODUCTION: The standard 4-minute application time for transcatheter cryoablation was determined in the 1990s when the system employed less potent chlorofluorocarbon refrigerants. The current refrigerant, nitrous oxide, generates substantially colder temperatures, with a faster cooling rate. METHODS AND RESULTS: We conducted a preclinical study on 32 mongrel dogs with stratified randomization of right atrial, right ventricular, and left ventricular chambers to 2-minute versus 4-minute application times using 8-mm electrode tip cryocatheters (Freezor Max, Medtronic CryoCath LP, Montreal, Canada). Animals were sacrificed one month after the procedure. Three-dimensional morphometric analyses were conducted in a blinded fashion. A total of 193 identified ablation lesions were processed for histological analyses, 102 with 2-minute applications and 91 with 4-minute applications. Ablation lesion surface area (167.8 ± 21.6 mm2 vs. 194.3 ± 22.6 mm2 , P = 0.40), maximum depth (4.4 ± 0.2 mm vs. 4.5 ± 0.2 mm, P = 0.71), and volume (125.7 ± 69.5 mm3 vs. 141.0 ± 83.5 mm3 , P = 0.25) were similar between groups. Overall, 90.2% of ablation lesions in the right atrium were transmural, 45.6% in the right ventricle, and 2.4% in the left ventricle, with no differences between 2-minute and 4-minute application times (P = 0.55). Thrombus was detected on the endocardial surface of 0.0% and 3.3% of ablation lesions created with 2-minute and 4-minute application times, respectively (P = 0.10). CONCLUSION: Single 2-minute and 4-minute application times result in catheter ablation lesions of similar size using the modern cryoablation system with nitrous oxide as a refrigerant. While these findings suggest the potential to reduce the standard 4-minute application time, further studies are required to compare clinical efficacy.

Clinical experience with a novel electromyographic approach to preventing phrenic nerve injury during cryoballoon ablation in atrial fibrillation.

BACKGROUND: Phrenic nerve palsy remains the most frequent complication associated with cryoballoon-based pulmonary vein (PV) isolation. We sought to characterize our experience using a novel monitoring technique for the prevention of phrenic nerve palsy. METHODS AND RESULTS: Two hundred consecutive cryoballoon-based PV isolation procedures between October 2010 and October 2013 were studied. In addition to standard abdominal palpation during right phrenic nerve pacing from the superior vena cava, all patients underwent diaphragmatic electromyographic monitoring using surface electrodes. Cryoablation was terminated on any perceived reduction in diaphragmatic motion or a 30% decrease in the compound motor action potential (CMAP). During right-sided ablation, a ≥30% reduction in CMAP amplitude occurred in 49 patients (24.5%). Diaphragmatic motion decreased in 30 of 49 patients and was preceded by a 30% reduction in CMAP amplitude in all. In 82% of cases, this reduction in CMAP amplitude occurred during right superior PV isolation. The baseline CMAP amplitude was 946.5±609.2 mV and decreased by 13.8±13.8% at the end of application. This decrease was more marked in the 33 PVs with a reduction in diaphragmatic motion than in those without (40.9±15.3% versus 11.3±10.5%; P<0.001). In 3 cases, phrenic nerve palsy persisted beyond the end of the procedure, with all cases recovering within 6 months. Despite the shortened application all veins were isolated. At repeat procedure the right-sided PVs reconnected less frequently than the left-sided PVs in those with phrenic nerve palsy. CONCLUSIONS: Electromyographic phrenic nerve monitoring using the surface CMAP is reliable, easy to perform, and offers an early warning to impending phrenic nerve injury.