Jessica R. Golbus

Feeding Complications in Hypoplastic Left Heart Syndrome After the Norwood Procedure: A Systematic Review of the Literature

Gastrointestinal and feeding complications after the Norwood procedure in infants with hypoplastic left heart syndrome increases morbidity and mortality. These problems are the result of intraoperative challenges, shunt-dependent physiology, and the absence of best-practice guidelines. In response, a systematic review of feeding-related complications and management strategies was performed. A literature search from 1950 to March 2010 identified 21 primary research articles and 4 reviews. Dysphagia, necrotizing enterocolitis (NEC), and poor nutritional status are significant feeding-related complications. Three studies directly compared the modified Blalock-Taussig shunt with the right ventricle-to-pulmonary artery conduit (RV-PA). Patients palliated with either shunt had impaired mesenteric blood flow. Mortality did not differ between shunt types. Three studies demonstrated improved outcomes, e.g., increased survival, decreased incidence of NEC, and decreased median time to recommended daily allowance of calories, with a postoperative feeding algorithm. Two studies showed increased survival between stage I and II surgical palliation after implementation of a home-monitoring system consisting of daily weight and systemic oxygen saturation measurements. The RV-PA shunt does not significantly alter mortality or increase mesenteric blood flow. A postoperative feeding algorithm and a home-monitoring system may improve outcomes and decrease average hospital length of stay (LOS). Additional studies are needed to determine which interventions, as part of a standardized protocol, improve survival and decrease complications.

Usefulness of peripheral vascular function to predict functional health status in patients with Fontan circulation.

After the Fontan operation, patients are at a substantial risk of the development of impaired functional health status. Few early markers of suboptimal outcomes have been identified. We sought to assess the association between peripheral vascular function and functional health status in Fontan-palliated patients. Asymptomatic Fontan patients (n = 51) and age- and gender-matched healthy controls (n = 22) underwent endothelial pulse amplitude testing using a noninvasive fingertip peripheral arterial tonometry (PAT) device. Raw data were transformed into the PAT ratio, an established marker of vascular function. Cardiopulmonary exercise testing was performed using the Bruce protocol. In the Fontan cohort, 94% of patients were New York Heart Association functional class I and 88% had a B-type natriuretic peptide level of <50 pg/ml. The baseline pulse amplitude, a measure that reflects the arterial tone at rest, was greater in the Fontan patients than in the controls (median 2.74, interquartile range 1.96 to 4.13 vs median 1.86, interquartile range 1.14 to 2.79, p = 0.03). The PAT ratio, a measure of reactive hyperemia, was lower in Fontan patients (median 0.17, interquartile range -0.04 to 0.44, vs median 0.50, interquartile range 0.27 to 0.74, p = 0.002). The key parameters of exercise performance, including peak oxygen consumption (median 28.8 ml/kg/min, interquartile range 25.6 to 33.2 vs median 45.5 ml/kg/min, interquartile range 41.7 to 49.9, p <0.0001) and peak work (median 192 W, interquartile range 150 to 246 vs median 330, interquartile range 209 to 402 W, p <0.0001), were lower in Fontan patients than in the controls. The PAT ratio correlated with the peak oxygen consumption (r = 0.28, p = 0.02) and peak work (r = 0.26, p = 0.03). In conclusion, in an asymptomatic Fontan population, there is evidence of reduced basal peripheral arterial tone and vasodilator response, suggesting dysfunction of the endothelium-derived nitric oxide pathway. Vasodilator function appears to correlate with exercise performance.

Successful cardiac transplantation outcomes in patients with adult congenital heart disease

Objectives The purpose of our study is (1) to characterise patients with congenital heart disease undergoing heart transplantation by adult cardiac surgeons in a large academic medical centre and (2) to describe successful outcomes associated with our multidisciplinary approach to the evaluation and treatment of adults with congenital heart disease (ACHD) undergoing orthotopic heart transplantation (OHT). Background Heart failure is the leading cause of death in patients with ACHD leading to increasing referrals for OHT. Methods The Penn Congenital Transplant Database comprises a cohort of patients with ACHD who underwent OHT between March 2010 and April 2016. We performed a retrospective cohort study of the 20 consecutive patients. Original cardiac diagnoses include single ventricle palliated with Fontan (n=8), dextro-transposition of the great arteries after atrial switch (n=4), tetralogy of Fallot (n=4), pulmonary atresia (n=1), Ebstein anomaly (n=1), unrepaired ventricular septal defect (n=1) and Noonan syndrome with coarctation of the aorta (n=1). Results Eight patients required pretransplant inotropes and two required pretransplant mechanical support. Nine patients underwent heart–liver transplant and three underwent heart–lung transplant. Three patients required postoperative mechanical circulatory support. Patients were followed for an average of 38 months as of April 2016, with 100% survival at 30 days and 1 year and 94% overall survival (19/20 patients). Conclusions ACHD–OHT patients require highly specialised, complex and multidisciplinary healthcare. The success of our programme is attributed to using team-based, patient-centred care including our multidisciplinary staff and specialists across programmes and departments.

Common and Rare Genetic Variation in CCR2, CCR5, or CX3CR1 and Risk of Atherosclerotic Coronary Heart Disease and Glucometabolic Traits.

Background— The chemokine receptors CCR2, CCR5, and CX3CR1 coordinate monocyte trafficking in homeostatic and inflammatory states. Multiple small human genetic studies have variably linked single nucleotide polymorphisms in these genes to cardiometabolic disease. We interrogated genome-wide association, exome sequencing, and exome array genotyping studies to ascertain the relationship between variation in these genes and coronary artery disease (CAD), myocardial infarction (MI), and glucometabolic traits. Methods and Results— We interrogated the CARDIoGRAMplusC4D (Coronary ARtery DIsease Genome wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics) (60 801 cases and 123 504 controls), the MIGen and CARDIoGRAM Exome consortia (42 335 cases and 78 240 controls), and Exome Sequencing Project and Early-Onset Myocardial Infarction (ESP EOMI; 4703 cases and 5090 controls) data sets to ascertain the relationship between common, low frequency, and rare variation in CCR2, CCR5, or CX3CR1 with CAD and MI. We did not identify any variant associated with CAD or MI. We then explored common and low-frequency variation in South Asians through Pakistan Risk of Myocardial Infarction Study (PROMIS; 9058 cases and 8379 controls), identifying 6 variants associated with MI including CX3CR1 V249I. Finally, reanalysis of the European HapMap imputed Diabetes Genetics Replication and Meta-Analysis (DIAGRAM), Global Lipids Genetics Consortium (GLGC), Genetic Investigation of Anthropometric Traits (GIANT), and Meta-Analysis of Glucose and Insulin-related Traits Consortium (MAGIC) data sets revealed no association with glucometabolic traits although 3 single nucleotide polymorphisms in PROMIS were associated with type II diabetes mellitus. Conclusions— No chemokine receptor variant was associated with CAD, MI, or glucometabolic traits in large European ancestry cohorts. In a South Asian cohort, we identified single nucleotide polymorphism associations with MI and type II diabetes mellitus but these did not meet significance in cohorts of European ancestry. These findings suggest the need for larger studies in South Asians but exclude clinically meaningful associations with CAD and glucometabolic traits in Europeans.

Polyneuropathy Associated with the Diffuse Infiltrative Lymphocytosis Syndrome

Diffuse infiltrative lymphocytosis syndrome (DILS) arises in HIV-positive patients secondary to infiltration of lymphocytes into the peripheral tissues and produces the disease’s characteristic symptoms—parotid gland enlargement and a sicca syndrome. Many patients, however, first seek medical attention for treatment of the extraglandular manifestations of DILS, most commonly interstitial pneumonitis. In this case report, we describe an atypical presentation of DILS characterized by polyradiculoneuropathy in the absence of parotid gland enlargement or interstitial pneumonitis. Minor salivary gland biopsy of the patient’s lip confirmed a chronic inflammatory state with lymphoid aggregates within the minor salivary glands. He was started on prednisone with immediate improvement in his symptoms. This report illustrates for clinicians the diverse extraglandular manifestations of DILS and underscores the importance of considering it in the differential diagnosis of HIV-positive patients with a preserved CD4 count who present with peripheral neuropathy.

Impact of Vitamin C on Endothelial Function and Exercise Capacity in Patients with a Fontan Circulation

OBJECTIVE   To evaluate the impact of antioxidant therapy on functional health status in Fontan-palliated patients. Design.  Prospective, randomized, double-blind, placebo-controlled trial. PATIENTS   Fifty-three generally asymptomatic Fontan patients. INTERVENTIONS   Patients were randomized to receive either high-dose ascorbic acid (vitamin C) or placebo for 4 weeks. OUTCOME MEASURES   Peripheral vascular function, as measured with endothelium-dependent digital pulse amplitude testing (EndoPAT), and exercise capacity were assessed before and after study drug treatment. Primary outcome measures included the EndoPAT index and peripheral arterial tonometry (PAT) ratio, both validated markers of vascular function. Secondary outcome measures included peak oxygen consumption and work. RESULTS   Twenty-three vitamin C- and 21 placebo-assigned subjects completed the protocol (83%). Median age and time from Fontan completion were 15 (interquartile range [IQR] 11.7-18.2) and 11.9 years (IQR 9.0-15.7), respectively. Right ventricular morphology was dominant in 30 (57%). Outcome measures were similar between groups at baseline. Among all subjects, vitamin C therapy was not associated with a statistical improvement in either primary or secondary outcome measures. In subjects with abnormal vascular function at baseline, compared with placebo, vitamin C therapy more frequently resulted in normalization of the EndoPAT index (45% vs. 17%) and PAT ratio (38% vs. 13%). CONCLUSIONS   Short-term therapy with vitamin C does not alter endothelial function or exercise capacity in an asymptomatic Fontan population overall. Vitamin C may provide benefit to a subset of Fontan patients with abnormal vascular function.