Christopher J. Danford

Long-term (5- to 20-year) outcomes after transcatheter or surgical treatment of hemodynamically significant isolated secundum atrial septal defect

Truly long-term follow-up data after transcatheter closure (TC) of atrial septal defects (ASDs) are scarce. We report the 5- to 20-year outcomes of TC and surgical closure (SC) for typical secundum ASD. We reviewed the records of patients with isolated secundum ASD and right ventricular volume overload who underwent TC or SC (January 1, 1986 to September 30, 2005). Follow-up was obtained through a combination of chart review, physician records, and telephone survey. We identified 375 patients (207 SC and 168 TC) and obtained follow-up data >5 years (median follow-up 10 years) for 300 (152 SC, 148 TC). Nine patients have died (3%). The New York Heart Association functional class was unchanged in 227 patients, improved in 25, and was worse in 15. Clinically significant arrhythmia was found in 28 patients (9.3%); 21% aged >40 years developed arrhythmia. On multivariate analysis, the odds of significant arrhythmia tended to be greater in the SC group, but this was statistically insignificant (95% confidence interval 0.68 to 3.9, p = 0.27). Age and preprocedure arrhythmia, but not TC or SC, were independent risk factors for late arrhythmia (p <0.001). No difference was found in the incidence of late, probably embolic, stroke in the TC (3%) versus SC (2%) groups. In conclusion, long-term outcomes after secundum ASD closure using modern methods are excellent. No significant differences were found between TC versus SC with regard to survival, functional capacity, atrial arrhythmias, or embolic neurologic events. Arrhythmia and neurologic events remain long-term risks after ASD closure, especially if the patient had pre-existing arrhythmia.

Main pulmonary artery dilation in association with congenital bicuspid aortic valve in the absence of pulmonary valve abnormality

Background Main pulmonary artery (MPA) dilation is reported to occur in association with pulmonary valve (PV) abnormalities and in genetic diseases of connective tissue. Aim To determine whether MPA dilation occurs with bicuspid aortic valve (BAV) in the absence of PV abnormality. Methods MPA and aortic dimensions were investigated in 194 subjects with BAV and 178 controls matched for age, sex and body surface area (BSA) using transthoracic two-dimensional echocardiography. Using control measurements, linear regression of each parameter versus age, gender, and BSA2/3 provided expected values. For each subject with BAV, the percentage divergence from expected value ((observed − expected value)/expected value) for each dimension was analysed. Results MPA and aortic measurements showed normal distribution in all subjects. PV annulus and MPA were larger in BAV; 17.7% positive divergence of MPA dimension from expected was found in diastole, and 16.7% in systole. Aortic dimensions at all levels measured were larger in BAV; divergence was greater distally than proximally (10% divergence at annulus, 31% at ascending aorta). In BAV, divergence of ascending aortic dimensions from expected values increased with age (r2=0.142, p=0.02), but MPA divergence from expected values did not increase with age (r2=0.001, p=0.296). Conclusions MPA dilation occurs in association with BAV in the absence of PV abnormality, suggesting primary vessel wall pathology predisposing to arterial dilation. A systemic abnormality of connective tissue common to both arteries may be responsible, or the dilation may result from a common developmental exposure as both originate from the embryologic cono-truncus.

Ultrasound contrast and real-time perfusion in conjunction with supine bicycle stress echocardiography for comprehensive evaluation of surgically corrected congenital heart disease

AIMS We sought to evaluate the efficacy of ultrasound contrast (UC) and low mechanical index real-time perfusion (RTP) in the haemodynamic and anatomic assessment of repaired congenital heart disease (CHD) at rest and during supine bicycle stress echocardiography (BSE). METHODS AND RESULTS Patients with CHD (n = 51, median age 21.5 years) were prospectively studied. All had compromised image quality, 20 (39%) had arrhythmias, and 10 (20%) had pacemakers. RTP was performed at rest and during BSE using Definity and Contrast Pulse Sequencing, with assessment of Doppler pressure gradients. Diagnoses included tetralogy of Fallot (n = 27), transposition of the great arteries (TGA) atrial switch (n = 10), TGA arterial switch (n = 2), aortic valve disease (n = 4), Fontan (n = 4), and Kawasaki disease (n = 4). UC with RTP improved endocardial border definition, with increased number of left ventricular (LV) and right ventricular (RV) segments visualized at rest (P < 0.0001) and during stress. LV ejection fraction (EF) and RV fractional area change (FAC) were measurable at rest and peak stress, RV FAC correlating closely with same-day magnetic resonance EFs (r = 0.72; P < 0.001). UC enhanced Doppler signals, enabling subpulmonary ventricular systolic pressure measurements at rest and stress. In six patients, marked elevations of subpulmonary ventricular systolic pressure were detected with UC during BSE, and quantifiable ventricular dysfunction. No adverse events occurred, other than transient low back pain in one patient. CONCLUSION UC at rest and with supine BSE enables safe and comprehensive assessment of anatomy, haemodynamics, and biventricular functional and perfusion reserve in adolescents and young adults with surgically modified CHD.

Risk factors for hepatocellular carcinoma in cirrhosis due to nonalcoholic fatty liver disease: A multicenter, case-control study

AIM To identify risk factors associated with hepatocellular carcinoma (HCC), describe tumor characteristics and treatments pursed for a cohort of individuals with nonalcoholic steatohepatitis (NASH) cirrhosis. METHODS We conducted a retrospective case-control study of a well-characterized cohort of patients among five liver transplant centers with NASH cirrhosis with (cases) and without HCC (controls). RESULTS Ninety-four cases and 150 controls were included. Cases were significantly more likely to be male than controls (67% vs 45%, P < 0.001) and of older age (61.9 years vs 58 years, P = 0.002). In addition, cases were more likely to have had complications of end stage liver disease (83% vs 71%, P = 0.032). On multivariate analysis, the strongest association with the presence of HCC were male gender (OR 4.3, 95%CI: 1.83-10.3, P = 0.001) and age (OR = 1.082, 95%CI: 1.03-1.13, P = 0.001). Hispanic ethnicity was associated with a decreased prevalence of HCC (OR = 0.3, 95%CI: 0.09-0.994, P = 0.048). HCC was predominantly in the form of a single lesion with regional lymph node(s) and distant metastasis in only 2.6% and 6.3%, respectively. Fifty-nine point three percent of individuals with HCC underwent locoregional therapy and 61.5% underwent liver transplantation for HCC. CONCLUSION Male gender, increased age and non-Hispanic ethnicity are associated with HCC in NASH cirrhosis. NASH cirrhosis associated HCC in this cohort was characterized by early stage disease at diagnosis and treatment with locoregional therapy and transplant.

Osteoporosis in primary biliary cholangitis

Primary biliary cholangitis (PBC) is an autoimmune cholestatic liver disease with multiple debilitating complications. Osteoporosis is a common complication of PBC resulting in frequent fractures and leading to significant morbidity in this population, yet evidence for effective therapy is lacking. We sought to summarize our current understanding of the pathophysiology of osteoporosis in PBC, as well as current and emerging therapies in order to guide future research directions. A complete search with a comprehensive literature review was performed with studies from PubMed, EMBASE, Web of Science, Cochrane database, and the Countway Library. Osteoporosis in PBC is driven primarily by decreased bone formation, which differs from the increased bone resorption seen in postmenopausal osteoporosis. Despite this fundamental difference, current treatment recommendations are based primarily on experience with postmenopausal osteoporosis. Trials specific to PBC-related osteoporosis are small and have not consistently demonstrated a benefit in this population. As it stands, prevention of osteoporosis in PBC relies on the mitigation of risk factors such as smoking and alcohol use, as well as encouraging a healthy diet and weight-bearing exercise. The primary medical intervention for the treatment of osteoporosis in PBC remains bisphosphonates though a benefit in terms of fracture reduction has never been shown. This review outlines what is known regarding the pathogenesis of bone disease in PBC and summarizes current and emerging therapies.

Encapsulating peritoneal sclerosis

Encapsulating peritoneal sclerosis (EPS) is a debilitating condition characterized by a fibrocollagenous membrane encasing the small intestine, resulting in recurrent small bowel obstructions. EPS is most commonly associated with long-term peritoneal dialysis, though medications, peritoneal infection, and systemic inflammatory disorders have been implicated. Many cases remain idiopathic. Diagnosis is often delayed given the rarity of the disorder combined with non-specific symptoms and laboratory findings. Although cross-sectional imaging with computed tomography of the abdomen can be suggestive of the disorder, many patients undergo exploratory laparotomy for diagnosis. Mortality approaches 50% one year after diagnosis. Treatment for EPS involves treating the underlying condition or eliminating possible inciting agents (i.e. peritoneal dialysis, medications, infections) and nutritional support, frequently with total parenteral nutrition. EPS-specific treatment depends on the disease stage. In the inflammatory stage, corticosteroids are the treatment of choice, while in the fibrotic stage, tamoxifen may be beneficial. In practice, distinguishing between stages may be difficult and both may be used. Surgical intervention, consisting of peritonectomy and enterolysis, is time-consuming and high-risk and is reserved for situations in which conservative medical therapy fails in institutions with surgical expertise in this area. Herein we review the available literature of the etiology, pathogenesis, diagnosis, and treatment of this rare, but potentially devastating disease.

Managing the Burden of Non-NASH NAFLD

Purpose of ReviewThe purpose of this review article is to raise awareness of the significance of steatosis that exists within the spectrum of non-alcoholic fatty liver disease (NAFLD). While the impact of non-alcoholic steatohepatitis (NASH) and its potential for histologic progression to cirrhosis and hepatocellular carcinoma is widely appreciated, the impact of non-NASH NAFLD (steatosis) on morbidity and mortality is less well recognized.Recent FindingsNAFLD is a spectrum of hepatic pathology with a rising prevalence worldwide. Steatosis without fibrosis carries a low risk of progression to cirrhosis but likely confers an increased risk of diabetes mellitus and cardiovascular disease.SummaryAbout a quarter of the world population is affected by NAFLD. NAFLD represents a burden to affected individuals and economics of the healthcare system and contributes significantly to morbidity and mortality worldwide. An increased level of awareness and knowledge about risk factors and diagnostic strategies is needed to identify patients affected with disease.

Clinical Implications of a Multivariate Stratification Model for the Estimation of Prognosis in Ventricular Septal Defect

OBJECTIVES To derive and validate a multivariate stratification model for prediction of survival free from intervention (SFFI) in ventricular septal defect (VSD). A secondary aim is for this model to serve as proof of concept for derivation of a more general congenital heart disease prognostic model, of which the VSD model will be the first component. STUDY DESIGN For 12 years, 2334 subjects with congenital heart disease were prospectively and consecutively enrolled. Of these, 675 had VSD and form the derivation cohort. One hundred seven other subjects with VSD followed in another practice formed the validation cohort. The derivation cohort was serially stratified based on clinical and demographic features correlating with SFFI. RESULTS Six strata were defined, the most favorable predicting nearly 100% SFFI at 10 years, and the least favorable, a high likelihood of event within weeks. Strata with best SFFI had many subjects with nearly normal physiology, muscular VSD location, or prior intervention. In the validation cohort, the relation between predicted and actual SFFI at 6 months, 1 year, 2 years, and 5 years follow-up had areas under the receiver operating characteristic curves 0.800 or greater. CONCLUSIONS A prediction model for SFFI in VSD has been derived and validated. It has potential for clinical application to the benefit of patients and families, medical trainees, and practicing physicians.