Targeted septal branch microcirculatory embolization with tris-acryl gelatin microspheres in hypertrophic obstructive cardiomyopathy

Background Alcohol septal ablation (ASA) has been shown to be an effective treatment in patients with hypertrophic obstructive cardiomyopathy (HOCM) who are refractory to medical treatment. ASA may cause some life-threatening complications including conduction disturbances, hemodynamic compromise, ventricular arrhythmias, distant and massive myocardial necrosis. Tris-acryl gelatin microspheres provide consistent and predictable results for effective targeted microcirculatory embolization. Purpose We aimed to report our initial experience in tris-acryl gelatin microspheres for septal ablation in HOCM. Methods Microspheres are biocompatible, hydrophilic, non-resorbable microspheres which are available in a range of calibrated sphere sizes. In our method, after the cannulation of the left anterior descending by a 6F-7F guiding catheter, a 0.014-inch guidewire is introduced through the catheter and advanced into the septal branch. This septal artery is selectively cannulated with a 4F catheter over the guidewire. Selective angiography of the septal artery is performed to show the anatomy and collateral branches to other coronary arteries. Contrast echocardiography is performed to make sure that the pertinent septal artery is the target vessel supplying the hypertrophied septum. A microcatheter is then advanced deep enough into the septal artery through the 4F catheter. Microspheres/contrast solution infused slowly under fluoroscopic guidance into the targeted septal branches initially using coronary arteriolar sized small particles (diameter 100–300 μm); then the particle size was stepped up to larger particles (diameter 300–500 μm) until a complete block of the arteriolar flow is achieved. Results Septal ablation with tris-acryl gelatin microspheres was performed in 6 patients (mean age = 47.8±11.5; 5 males). Immediately after the procedure peak left ventricular outflow (LVOT) gradient reduced significantly both for direct catheter (69.0±13.8 vs. 8.2±3.7 mmHg, P<0.001) and Doppler echocardiographic measurements (78.8±19.9 vs. 12.0±5.1 mmHg, P<0.001). Post-procedure peak serum CK- MB fraction concentration was 82±22 ng/ml (reference range is 0 - 4.9 ng/mL) and peak serum troponin T concentration was 1.2 ng/ml [(interquartile range, 0.4–1.4), (reference range is 0 - 0.017 ng/mL)]. LVOT tract gradient reduction persisted after 6 months follow-up. There was no significant complication during the procedure and within a 6 months follow-up period. Conclusions The novel strategy by targeted septal branch microcirculatory embolization with tris-acryl gelatin microspheres seems to be an efficient and safe approach to HOCM. Further experience is needed in order to assess the long-term efficacy and safety of this technique. Funding Acknowledgement Type of funding source: None

Predictors of 90-Day Mortality following Hepatic Resection for Hepatocellular Carcinoma

<b><i>Background/Purpose:</i></b> 90-day mortality is a key performance indicator for short-term perioperative outcome of hepatic resection (HR). Although many preoperative, intraoperative, and postoperative variables predict 90-day mortality following elective HR, only few are specific to hepatocellular carcinoma (HCC). This study aims to determine the predictors of 90-day mortality following elective HR for HCC. <b><i>Methods:</i></b> We report a retrospective analysis of patients who underwent elective HR between January 1, 2007, and December 31, 2017. Health status, perioperative variables, and the presence of post-hepatectomy liver failure (PHLF) were studied. Cox’s regression evaluated factors predicting 90-day mortality. <b><i>Results:</i></b> Two hundred and forty-four patients diagnosed with HCC underwent HR; 102 (41.8%) underwent a major HR. The postoperative 90-day mortality rate was 5.3%. Multivariate analysis demonstrated that Child-Pugh score (<i>p</i> &#x3c; 0.001), intraoperative blood loss (<i>p</i> = 0.013), the 50-50 criteria for PHLF (<i>p</i> &#x3c; 0.001) on postoperative day 5, and peak serum bilirubin &#x3e;119 µmol/L (<i>p</i> = 0.007) on postoperative day 3 predict 90-day mortality. <b><i>Conclusion:</i></b> In patients with HCC undergoing HR, Child-Pugh score, intraoperative blood loss, the 50-50 criteria for PHLF on postoperative day 5, and peak serum bilirubin &#x3e;119 µmol/L on postoperative day 3 predict 90-day mortality following elective HR for HCC.

The Impact of Hypernatremia in Preterm Infants on Neurodevelopmental Outcome at 18 Months of Corrected Age

Objective The study objective was to assess the correlation between hypernatremia during the first week of life and neurodevelopmental outcomes at 18 months of corrected age in premature infants. Study Design A retrospective observational study of preterm infants born at less than 32 weeks of gestation who had a neurodevelopmental assessment with the Bayley scales of infant and toddler development III at 18 ± 6 months of corrected age. Serum sodium levels from birth through 7 days of life were collected. The study cohort was divided into two groups: infants with a peak serum sodium of >145 mmol/L (hypernatremia group) and infants with a peak serum sodium level of <145 mmol/L (no hypernatremia group). Prenatal, intrapartum, and postnatal hospital course and neurodevelopmental data at 18 ± 6 months were collected. Logistic regression analysis was used to assess the correlation between neonatal hypernatremia and neurodevelopment with adjustment for selected population characteristics. Results Eighty-eight preterm infants with complete neurodevelopmental outcome data at 18 ± 6 months of corrected gestational age were included in the study. Thirty-five neonates were in the hypernatremia group and 53 were in the no hypernatremia group. Maternal and neonatal characteristics were similar between the two groups except that the hypernatremia group had a significantly lower average birth weight and gestational age. Comparison of the mean neurodevelopmental scores between the two groups showed that patients in the hypernatremia group as compared with those in the no hypernatremia group had significantly lower neurodevelopmental scaled scores in the fine motor domain (p = 0.01). This difference remained significant (p = 0.03, odds ratio [OR] = 0.8, 95% confidence interval [CI]: 0.6–0.97) when adjusted for birth weight and gestational age. Conclusion Preterm infants born at less than 32 weeks of gestation with hypernatremia in the first week of life have lower fine motor scores at 18 months of corrected age. Key Points

Natural History of Adrenal Steroidogenesis in Autoimmune Addison’s Disease Following Diagnosis and Treatment

Context The natural history of adrenal function in autoimmune Addison disease once diagnosed and treated has not been systematically studied, but several case reports of recovery from established adrenal failure suggest it may not be uniform. Objective To ascertain steroidogenic function in autoimmune Addison disease immediately following diagnosis and during prolonged treatment. Design We studied peak serum cortisol in response to ACTH1-24 in 20 newly diagnosed autoimmune Addison disease patients at first presentation and then again within a month. We also studied 37 patients with established Addison disease (for between 7 months and 44 years) in a medication-free state, measuring peak serum cortisol responses to ACTH1-24 and the urine LC-MS steroid metabolome. Results Adrenal steroidogenesis declined rapidly after steroid replacement treatment for newly diagnosed Addison disease was started, with a peak serum cortisol falling from 138 ± 19 nmol/L (SEM) at presentation to 63 ± 13 nmol/L over 4 weeks (P &lt; 0.003). Six of 37 participants (16%) with established Addison disease had detectable serum cortisol and urine glucocorticoid and mineralocorticoid metabolites during repeat testing, indicating variable degrees of residual adrenal function. Conclusion Autoimmune Addison disease is a heterogeneous condition, showing a rapid decline in adrenal steroidogenesis during the first few weeks following diagnosis, but low-level residual function in a minority of patients, which appears to persist for many years.

SAT-052 A Novel Oral Testosterone Therapy (TLANDO) Safely Restores Testosterone to Eugonadal Levels with Fixed Dose Treatment

Most testosterone (T) replacement therapy (TRT) products have relied on dose titration to achieve eugonadal levels. However, dose titration in clinical practice can be time-consuming, expensive, and subject to errors. TLANDO (LPCN 1021) is a novel oral testosterone undecanoate (TU) product absorbed via the intestinal lymphatic pathway. A previous clinical study (NCT02081300) suggested that titration with TLANDO has little to no impact to improve PK profiles. The objective of this study was to assess whether fixed dose of TLANDO can restore testosterone to eugonadal levels. A 24 day, open-label, single-arm, multicenter study with TLANDO in hypogonadal men (NCT03242590) was conducted. Subjects (N=95) received 225 mg testosterone undecanoate orally twice a day (i.e., 30 minutes after morning and evening meals) for 24 days. On Day 24, blood samples were collected over a 24 hour period. The primary endpoint was the percentage of TLANDO-treated subjects who achieved a 24-hour average serum T concentration within the eugonadal range of 300 to 1080 ng/dL after 24 days of treatment. Mean peak serum T concentration was calculated based on daily TLANDO administration at Day 24. Key safety endpoints included incidence of adverse events (AEs), physical examination results, clinical laboratory test results, and changes in HCT, lipids, and PSA. Treatment compliance was calculated as a percentage of the amount of study drug used divided by the amount of study drug expected to be used. 94 subjects completed the study with mean age of 56.0 years, mean BMI 32.8 kg/m2, and baseline T level 202 ± 75 ng/dL. 80% of subjects achieved a 24-hour average serum T concentration within the normal range at Day 24. The lower and upper bounds of the 95% confidence interval was 72% and 88% respectively. Following daily administration of TLANDO at Day 24, the mean peak serum T concentration was 1178 ± 484 ng/dL. The incidence of treatment emergent adverse events (TEAEs) was 21%. The most frequently reported TEAEs were blood prolactin increase (6.3%), weight increase (2.1%), headache (2.1%), and musculoskeletal pain (2.1%). No deaths were reported during the study. Increase in hematocrit (0.9%) and PSA (0.2 μg/L) was observed. Decrease in lipids was observed (-6.9 mg/dL for HDL, -1.5 mg/dL for LDL, -8.9 mg/dL for triglycerides, and -10.6 mg/dL for total cholesterol). Overall mean treatment compliance was 99.7 ± 4.9%. In conclusion, a twice-daily, fixed-dose of TLANDO (450 mg TU total daily dose) successfully achieved target serum T level and achieved a safety profile consistent with that of other approved TRT products.