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Background Transcatheter aortic valve replacement (TAVR) is now indicated in patients with symptomatic aortic stenosis and low, moderate, and high surgical risk. There are multiple types of valves available in TAVR. SAPIEN 3, and Evolut R are two of the most commonly used valves. Methods We conducted a systematic review and meta-analysis of all studies that compared SAPIEN 3 vs Evolut R in patients undergoing TAVR. The primary endpoint of this meta-analysis was 30-day mortality. Secondary outcomes included major of life-threatening bleeding, risk of stroke, need of permanent pacemaker implantation, and risk of moderate to severe paravalvular regurgitation (PVR). Results We included a total of 9 studies. One study was a randomized clinical trial, five were prospective observational studies and three were retrospective. 30-day mortality rate was similar between SAPIEN 3 and Evolut R (odds ratio (OR) 1.19; 95% confidence interval (CI) 0.72 to 1.93; p = 0.47). The risk of major or life-threatening bleeding (OR of 0.83, 95% CI 0.50 to 1.39; p = 0.48), and the risk of stroke (OR of 0.82, 95% CI 0.38 to 1.78; p = 0.62) were also similar between the two types of valves. Compared to SAPIEN 3, Evolut R was associated with statistically significant risk of permanent pacemaker implantation (OR of 1.40, 95% CI 1.15 to 1.70; p = 0.0007), and moderate to severe PVR (OR of 2.56, 95% CI 1.14 to 5.74; p = 0.02). Conclusions At 30 day follow up, both Evolut R and SAPIEN 3 shared similar risks of 30-day mortality, major or life-threatening bleeding, and stroke; however greater odds of pacemaker placement implantation and moderate to severe PVR were associated with Evolut R.

There is rising use of recreational nitrous oxide (N₂O) in the community because of its availability as “whippet” canisters. Nitrous oxide use is still legal and outside the purview of the Drug Enforcement Administration (DEA). It is not detected on a routine drug screen, and patient history is key to establishing the diagnosis. We highlight a case of subacute combined degeneration in a young patient secondary to recreational nitrous oxide use, which improved with vitamin B12 replacement. A 19-year-old male with a history of recreational nitrous oxide use presented with progressive bilateral lower extremity paresthesia and ataxia. Neurological examination revealed deficits in vibration and proprioception, motor weakness, and diminished reflexes in the bilateral lower extremities. The laboratory results were significant for pancytopenia, profound vitamin B12 deficiency (55 ng/mL), and elevated methylmalonic acid (2.14 umol/L). The urine drug screen was negative. MRI showed subacute degeneration of the spinal cord dorsal column at C2-C5. Treatment with intramuscular cyanocobalamin resulted in the normalization of pancytopenia and B12 levels (573 ng/mL). The patient had partial resolution of neurological symptoms following the initiation of parenteral vitamin B12 replacement. The mechanism of subacute combined degeneration in the setting of nitrous oxide toxicity appears to be mediated by functional B12 deficiency. Oxidation of cobalt ion of vitamin B12 by nitrous oxide renders it unavailable as a coenzyme, leading to the accumulation of by-products that enter lipid metabolism, resulting in abnormal myelin synthesis, which ultimately manifests as subacute combined degeneration. Vitamin B12 deficiency of unclear etiology should raise suspicion for nitrous oxide toxicity as early initiation of replacement therapy with vitamin B12 can improve neurological function.

Introduction: Short QT syndrome (SQTS) is a very rare genetic disease of the electrical system of the heart which is associated with an increase risk of abnormal cardiac rhythms and sudden cardiac death. First described in 2000 with the first genetic mutation associated with SQTS described in 2004. We present a case of Short QT syndrome in a 53 year old male. Case: A 53 year old male with a PMH of HTN, alcohol abuse, and tobacco dependence presented to the ED with palpitations. Patient endorsed that he was in his usual state of health the day prior to arrival. He went to bed after drinking alcohol and woke up suddenly pale and diaphoretic with dyspnea and a persistent feeling of impending doom. On arrival to the ED, he was tachypneic (26 breaths/min) with a heart rate of 163 bpm and a blood pressure of 100/80 mmHg. EKG showed atrial fibrillation with RVR. The patient converted to normal sinus rhythm after one dose of IV Cardizem 10 mg was administered for rate control. The next day he had multiple episodes of Torsades de Pointe and monomorphic ventricular tachycardia treated with synchronized cardioversion, 2g of magnesium, IV amiodarone and lidocaine drip. He was transferred to the ICU for further evaluation and monitoring. Repeat EKG showed normal sinus rhythm at 75 bpm and short QT (QT= 328). TTE showed normal biventricular size and function (LVEF 60-65%) with no valvular abnormalities. Dual chamber Implantable Cardioverter Defibrillator (ICD) was placed and outpatient genetic testing was scheduled. Discussion: SQTS is very rare with roughly 70 cases identified worldwide since the condition was discovered in 2000. It is a congenital channelopathy related to potassium channels and represented by a normal heart rate with accelerated cardiac repolarization. Normal QT range is 350-440 msec while SQTS range is 210-340 msec. Mutations in the KCNH2, KCNJ2, or KCNQ1 genes lead to enhanced flow of potassium ions across the membrane of cardiac muscle cells. Patients can present at any age with palpitations, syncope, atrial fibrillation, and sudden cardiac death. The cornerstone to diagnosing SQTS is an electrocardiogram. Patients with SQTS can be managed with ICD implantation, quinidine (especially with KCNH2 mutation), and sotalol (with other mutations other than KCNH2).

The Marfan syndrome (MFS) patients are highly predisposed to thoracic aortic aneurysm and/or dissection, with virtually every patient having evidence of aortic disease at some point during their lifetime. We conducted a meta-analysis to investigate the efficacy of angiotensin receptor blockers (ARBs) in slowing down the progression of aortic dilatation in MFS patients. PUBMED, EMBASE, and COCHRANE databases were searched for relevant articles published from inception to February 1, 2020. We included randomized clinical trials evaluating the effect of ARBs on aortic root size in patients with MFS with a follow-up period of at least 2.5 years. Seven studies were included with a total of 1,510 patients. Our analysis demonstrated a significantly smaller change in aortic root and ascending aorta dilation in the ARBs treated group when compared with placebo (mean difference 0.68; 95% confidence interval [CI] −1.31 to −0.04; p = 0.04, I2 = 94%, and mean difference −0.13, 95% CI −0.17 to −0.09; p

Loss-of-function mutations of the s-cell ATP-sensitive potassium channels (KATP) cause the most common and severe form of congenital hyperinsulinism (KATPHI), a disorder of s-cell function characterized by severe hypoglycemia. Children with KATPHI are typically unresponsive to medical therapy and require pancreatectomy for intractable hypoglycemia. We tested the hypothesis that inhibition of insulin receptor signaling may prevent hypoglycemia in KATPHI. To test this hypothesis, we examined the effect of an antibody allosteric inhibitor of the insulin receptor, XMetD, on fasting plasma glucose in a mouse model of KATPHI (SUR-1-/- mice). SUR-1-/- and wild-type mice received twice weekly intraperitoneal injections of either XMetD or control antibody for 8 wks. Treatment with XMetD significantly decreased insulin sensitivity, and increased hepatic glucose output and fasting plasma glucose. These findings support the potential use of insulin receptor antagonists as a therapeutic approach to control the hypoglycemia in congenital hyperinsulinism.

Loss-of-function mutations of the ß-cell ATP-sensitive potassium channels (K(ATP)) cause the most common and severe form of congenital hyperinsulinism (K(ATP)HI), a disorder of ß-cell function characterized by severe hypoglycemia. Children with K(ATP)HI are typically unresponsive to medical therapy and require pancreatectomy for intractable hypoglycemia. We tested the hypothesis that inhibition of insulin receptor signaling may prevent hypoglycemia in K(ATP)HI. To test this hypothesis, we examined the effect of an antibody allosteric inhibitor of the insulin receptor, XMetD, on fasting plasma glucose in a mouse model of K(ATP)HI (SUR-1(−)(/)(−) mice). SUR-1(−)(/)(−) and wild-type mice received twice weekly intraperitoneal injections of either XMetD or control antibody for 8 wks. Treatment with XMetD significantly decreased insulin sensitivity, and increased hepatic glucose output and fasting plasma glucose. These findings support the potential use of insulin receptor antagonists as a therapeutic approach to control the hypoglycemia in congenital hyperinsulinism.

Background/Aims: Dumping syndrome is a common complication in children after fundoplication and other gastric surgeries and is characterized by postprandial hypoglycemia (PPH). Children with PPH have an exaggerated GLP-1 response to a meal with an exaggerated insulin surge and subsequent hypoglycemia. We evaluated the role of GLP-1 in the pathogenesis of PPH by examining the effects of GLP-1 receptor blockade on glucose and insulin response to a meal. Methods: Six children with known PPH after surgery underwent a mixed meal tolerance test with/without the GLP-1 receptor antagonist exendin-(9-39) using an open-label crossover design. Results: Average nadir plasma glucose concentration was ≥65 mg/dl in all treatment conditions; however, 3 out of the 6 subjects had a nadir plasma glucose Conclusion: Our results suggest that the exaggerated insulin response to a meal is at least in part due to the effects of GLP-1 on the pancreatic β-cell and suggest that GLP-1 receptor antagonists may represent a potential avenue of treatment for children with PPH.