Hepatocellular carcinoma and the Fontan circulation: Clinical presentation and outcomes.

BACKGROUND: Fontan-associated liver disease (FALD) is universal in patients with a Fontan circulation. Hepatocellular carcinoma (HCC) is one of its severe expressions, and, though rare, frequently fatal. The purpose of this study was to describe the clinical presentation, risk factors, and outcomes of HCC in patients with a Fontan circulation. METHODS: A multicenter case series of Fontan patients with a diagnosis of HCC formed the basis of this study. The case series was extended by published cases and case reports. Clinical presentation, tumor characteristics, laboratory and hemodynamic findings as well as treatment types and outcomes, were described. RESULTS: Fifty-four Fontan patients (50% female) with a diagnosis of HCC were included. Mean age at HCC diagnosis was 30 ± 9.4 years and mean duration from Fontan surgery to HCC diagnosis was 21.6 ± 7.4 years. Median HCC size at the time of diagnosis was 4 cm with a range of 1 to 22 cm. The tumor was located in the right hepatic lobe in 65% of the patients. Fifty-one percent had liver cirrhosis at the time of HCC diagnosis. Fifty percent of the patients had no symptoms related to HCC and alpha-fetoprotein was normal in 26% of the cases. Twenty-six patients (48%) died during a median follow-up duration of 10.6 (range 1-50) months. CONCLUSIONS: HCC in Fontan patients occurs at a young age with a 1-year survival rate of only 50%. Meticulous liver surveillance is crucial to detect small tumors in the early stage.

Acute Pulmonary Embolism: Contemporary Approach to Diagnosis, Risk-Stratification, and Management.

Pulmonary embolism (PE) affects over 300,000 individuals each year in the United States and is associated with substantial morbidity and mortality. Improvements in the diagnostic performance and availability of computed tomographic pulmonary angiography and D-dimer testing have facilitated the evaluation of patients with suspected PE. High clinical suspicion is required in those with risk factors and/or those that manifest signs or symptoms of venous thromboembolic disease, with validated clinical risk scores such as the Wells and modified Wells score or the PE rule-out criteria helpful in estimating the likelihood for PE. For those with confirmed PE, patients should be categorized and triaged according to the presence or absence of shock or hypotension. Normotensive patients can be further risk-stratified using validated prognostic risk scores, as well as by using imaging and cardiac biomarkers, with those having either signs of right ventricular dysfunction on imaging studies and/or abnormal cardiac biomarkers categorized as being at intermediate-risk and requiring close monitoring and hospital admission. Early discharge and/or home therapy are possible in those that do not manifest any high-risk features. The initial treatment for most patients that are stable consists of anticoagulation, with advanced therapies such as thrombolysis, catheter-based therapies, or surgical embolectomy deferred for those at high risk. Given the heterogeneous presentations of PE and various management strategies available, the development of multidisciplinary PE response teams has emerged to help facilitate decision-making in these patients.

Vasopressor magnitude predicts poor outcome in adults with congenital heart disease after cardiac surgery.

BACKGROUND: High levels of vasoactive inotrope support (VIS) after congenital heart surgery are predictive of morbidity in pediatric patients. We sought to discern if this relationship applies to adults with congenital heart disease (ACHD). METHODS: We retrospectively studied adult patients (≥18 years old) admitted to the intensive care unit after cardiac surgery for congenital heart disease from 2002 to 2013 at Mayo Clinic. Vasoactive medication dose values within 96 hours of admission were examined to determine the relationship between VIS score and poor outcome of early mortality, early morbidity, or complication related morbidity. RESULTS: Overall, 1040 ACHD patients had cardiac surgery during the study time frame; 243 (23.4%) met study inclusion criteria. Sixty-two patients (25%), experienced composite poor outcome [including eight deaths within 90 days of hospital discharge (3%)]. Thirty-eight patients (15%) endured complication related early morbidity. The maximum VIS (maxVIS) score area under the curve was 0.92 (95% CI: 0.86-0.98) for in-hospital mortality; and 0.82 (95% CI: 0.76-0.89) for combined poor clinical outcome. On univariate analysis, maxVIS score ≥3 was predictive of composite adverse outcome (OR: 14.2, 95% CI: 7.2-28.2; P < 0.001), prolonged ICU LOS ICU LOS (OR: 19.2; 95% CI: 8.7-42.1; P < 0.0001), prolonged mechanical ventilation (OR: 13.6; 95% CI: 4.4-41.8; P < 0.0001) and complication related morbidity (OR: 7.3; 95% CI: 3.4-15.5; P < 0.0001). CONCLUSIONS: MaxVIS score strongly predicted adverse outcomes and can be used as a risk prediction tool to facilitate early intervention that may improve outcome and assist with clinical decision making for ACHD patients after cardiac surgery.

Benign nodules in post-Fontan livers can show imaging features considered diagnostic for hepatocellular carcinoma.

PURPOSE: To describe the imaging appearance of hyperenhancing nodules arising in post-Fontan patients and to identify specific features best correlated with malignancy. METHODS: Hyperenhancing hepatic nodules visible on CT and/or MRI in post-Fontan patients were identified retrospectively and reviewed by subspecialty radiologists. Nodules with characteristic imaging findings of focal nodular hyperplasia (FNH) were defined as typical, the remainder were defined as atypical, described in detail according to LIRADS criteria, and length of stability over time was recorded. Clinical data, alpha fetoprotein levels (AFP), central venous pressures (CVP), and histopathology were recorded. RESULTS: 245 hyperenhancing nodules (215 typical, 30 atypical) were evaluated in 30 patients. Twenty-nine atypical nodules showed washout (portal phase in 6, delayed phase in 29), 0 showed pseudocapsule, 1 showed threshold growth, 1 showed tumor in vein, and 5 showed ancillary features favoring malignancy. Pathology confirmed hepatocellular carcinoma (HCC) in 3 atypical nodules and FNH-like histology in 3 atypical and 4 typical nodules. 2 atypical nodules were present in a patient with clinical diagnosis of HCC. 20 nodules (7 typical, 13 atypical due to washout) were studied with hepatobiliary contrast agent and all showed homogenous hepatobiliary phase retention. Atypical nodules were significantly more likely to be HCC than biopsy-proven FNH-like or stable ≥24 months when showing portal phase washout (P < 0.001), mosaic architecture (P = 0.020) or in the presence of cirrhosis (P = 0.004) or elevated AFP (P = 0.004). Atypical nodules that were HCC had higher median CVP than those that were FNH-like (19, range 16-27 vs. 13, range 12-16 mmHg, P = 0.0003), there was not a significant difference based on median patient age (HCC 30, range 10-41 vs. FNH-like 40 range 10-41, P = 0.244). CONCLUSIONS: Benign hyperenhancing masses in Fontan patients may demonstrate washout and be mistaken for HCC by imaging criteria. Portal phase washout, mosaic architecture, elevated AFP and higher CVP were associated with HCC in the atypical nodules found in this population.

Intravascular and hybrid intraoperative stent placement for baffle obstruction in transposition of the great arteries after atrial switch.

OBJECTIVES: To report our experience with intravascular and hybrid intra-operative stent placement for baffle obstruction in patients with complete transposition of the great arteries (TGA) after the atrial switch (Mustard/Senning) operation. BACKGROUND: Venous baffle obstruction is a challenging complication after atrial switch operation in patients with TGA. Traditional treatment options include intravascular stenting or surgery. METHODS: A retrospective analysis of Mayo Clinic's electronic medical record was completed to identify consecutive pediatric and adult patients with TGA after atrial switch who underwent baffle stent implantation from 1994 to 2015. RESULTS: Overall, 64 patients were referred for cardiac catheterization, in whom 47 (73%) were noted to have hemodynamic and angiographic evidence of baffle obstruction. A total of 20 patients mean age 33 (range: 8-46) years old underwent stent implantation of baffle stenosis at a mean of 33 (range: 7.5-45) years after initial atrial switch operation (Mustard, n = 19; Senning, n = 1). Overall, 27 baffles were stented in 20 patients via the following approaches: intravascular (17); hybrid surgical (3); staged intravascular & hybrid (2). Sites of stent placement were: superior vena cava (SVC) (13); inferior vena cava (IVC) (9); pulmonary venous baffle (5). Three patients had stent placement in the SVC and IVC baffles during the same procedure. Procedural adverse events occurred in 2/22 cases (9%) including creation of unintentional baffle leak (n = 1) and stent migration (n = 1). There was no procedure-related mortality. At follow-up (median 2, range 0.02-10 years), significantly improved NYHA class and mean Doppler baffle gradient were demonstrated (P < 0.05). Mild baffle re-stenosis (mean Doppler gradient; 2-3 mmHg) occurred in two patients who have not required re-intervention. Trivial baffle leak was noted in four patients. Baffle re-intervention was only occurred in one patient. One patient with pre-procedural Class IV symptoms died 3.5 months after stent implantation. CONCLUSIONS: This study is the largest reported experience of intravascular and intra-operative hybrid stent placement for patients with TGA after atrial switch. Transcatheter and minimally invasive hybrid intraoperative surgical stent placement are an effective strategy for relief of systemic and pulmonary venous baffle obstruction. © 2016 Wiley Periodicals, Inc.

Cone Reconstruction of Atypical Ebstein Anomaly Associated with Right Ventricular Apical Hypoplasia.

Cone reconstruction for tricuspid valve repair has revolutionized the surgical treatment of Ebstein anomaly. We present the case of a 58-year-old woman with atypical Ebstein anomaly and right ventricular apical hypoplasia who was spared from palliative shunt physiology by our use of cone reconstruction. Compared with other techniques, cone reconstruction of the tricuspid valve more closely replicates normal valvular anatomy and function. This surgical procedure can be applied to many anatomic variations of Ebstein anomaly, as in our patient's apparently unique instance of atypical Ebstein anomaly with right ventricular apical hypoplasia.

Liver Disease in Patients After the Fontan Operation.

We reviewed records of all patients with an initial Fontan operation or revision from 1973 to 2012 at our institution (n = 1,138); 195 patients had postoperative liver data available. Cirrhosis was identified by histopathology or characteristic findings on imaging with an associated diagnosis of cirrhosis by a hepatologist. Of 195 patients with biopsy or imaging, 10-, 20-, and 30-year freedom from cirrhosis was 99%, 94%, and 57%, respectively. There were 40 of 195 patients (21%) diagnosed with cirrhosis (mean age at Fontan 10.7 ± 8 years). On multivariate analysis, hypoplastic left heart syndrome was associated with increased risk of cirrhosis (n = 2 of 16, p = 0.0133), whereas preoperative sinus rhythm was protective (p = 0.009). Survival after diagnosis of cirrhosis was 57% and 35%, at 1, and 5 years, respectively. The cause of death was known for 9 patients (5 multiorgan failure, 2 liver failure, and 2 heart failure). In conclusion, there is an incremental occurrence of cirrhosis after the Fontan, which should be considered when designing follow-up protocols for patients after Fontan operation.

Bioprosthetic Valve Thrombosis Versus Structural Failure: Clinical and Echocardiographic Predictors.

BACKGROUND: Bioprosthetic valve thrombosis (BPVT) is considered uncommon; this may be related to the fact that it is often unrecognized. Recent data suggest that BPVT responds to vitamin K antagonists, emphasizing the need for reliable diagnosis. OBJECTIVES: This study sought to determine the diagnostic features of BPVT and to formulate a diagnostic model for BPVT. METHODS: Cases of BPVT occurring between 1997 and 2013 were identified from the Mayo Clinic pathology database. Patients with BPVT were matched 1:2 for age, sex, and prosthesis position with patients whose valves were explanted for structural failure. We formulated a diagnostic model for BPVT using multivariate linear logistic regression and receiver operating characteristic. RESULTS: Among 397 consecutive cases of explanted bioprostheses, there were 46 cases of BPVT (11.6%; aortic 29, mitral 9, tricuspid 7, pulmonary 1), mean age was 63 years, and 68% were male. Thirty (65%) cases occurred >12 months post-implantation; median bioprosthetic valve longevity was 24 months (cases) versus 108 months (controls) (p < 0.001). Independent predictors of BPVT were >50% increase in mean echo-Doppler gradient from baseline within 5 years (odds ratio [OR]: 12.7), paroxysmal atrial fibrillation (OR: 5.19), subtherapeutic international normalized ratio (OR: 7.37), increased cusp thickness (OR: 12.2), and abnormal cusp mobility (OR: 6.94). Presence of all 5 diagnostic features was predictive of BPVT with 76% sensitivity, 93% specificity, 85% positive predictive value, and 89% negative predictive value (p < 0.001). CONCLUSIONS: BPVT is not uncommon and can occur several years after surgery. A combination of clinical and echocardiographic features can reliably diagnose BPVT.

Liver Nodules after the Fontan Operation: Role of Magnetic Resonance Elastography.

Hepatic dysfunction after the Fontan surgical palliation runs an indolent course. Moreover, there is no standard method of evaluating hepatic dysfunction. Magnetic resonance elastography has emerged as an advanced screening tool for preclinical detection of hepatic fibrosis and cirrhosis. We describe the case of a patient who had undergone Fontan palliation, and then developed liver nodules and elevated tumor markers 18 years later. Her case illustrates the challenges in diagnostic management of hepatic dysfunction and the potential role of magnetic resonance elastography in monitoring these patients.

Magnetic Resonance Elastography: A Novel Technique for the Detection of Hepatic Fibrosis and Hepatocellular Carcinoma After the Fontan Operation.

OBJECTIVE: To evaluate the utility of magnetic resonance elastography (MRE) in screening patients for hepatic fibrosis, cirrhosis, and hepatocellular carcinoma after the Fontan operation. PATIENTS AND METHODS: Hepatic MRE was performed in conjunction with cardiac magnetic resonance imaging in patients who had undergone a Fontan operation between 2010 and 2014. Liver stiffness was calculated using previously reported techniques. Comparisons to available clinical, laboratory, imaging, and histopathologic data were made. RESULTS: Overall, 50 patients at a median age of 25 years (range, 21-33 years) who had undergone a Fontan operation were evaluated. The median interval between Fontan operation and MRE was 22 years (range, 16-26 years). The mean liver stiffness values were increased: 5.5 ± 1.4 kPa relative to normal participants. Liver stiffness directly correlated with liver biopsy-derived total fibrosis score, time since operation, mean Fontan pressure, γ-glutamyltransferase level, Model for End-Stage Liver Disease score, creatinine level, and pulmonary vascular resistance index. Liver stiffness was inversely correlated with cardiac index. All 3 participants with hepatic nodules exhibiting decreased contrast uptake on delayed postcontrast imaging and increased nodule stiffness had biopsy-proven hepatocellular carcinoma. CONCLUSION: The association between hepatic stiffness and fibrosis scores, Model for End-Stage Liver Disease scores, and γ-glutamyltransferase level suggests that MRE may be useful in detecting (and possibly quantifying) hepatic cirrhosis in patients after the Fontan operation. The correlation between stiffness and post-Fontan time interval, mean Fontan pressure, pulmonary vascular resistance index, and reduced cardiac index suggests a role for long-term hepatic congestion in creating these hepatic abnormalities. Magnetic resonance elastography was useful in detecting abnormal nodules ultimately diagnosed as hepatocellular carcinoma. The relationship between stiffness with advanced fibrosis and hepatocellular carcinoma provides a strong argument for additional study and broader application of MRE in these patients.

IL-6 and its receptors in coronary artery disease and acute myocardial infarction.

Biomarkers such as interleukin-6 (IL-6), soluble interleukin-6 receptor (sIL-6R), and high sensitive C-reactive protein (hsCRP) have been reported to be elevated in acute myocardial infarction (AMI). The aim of this study is to determine the relationship between these markers during AMI, as well as their relationship to clinical parameters in an effort to discern their predictive potential in cardiac events. Serum was collected from 73 patients with; AMI, stable coronary artery disease (CAD), and controls during cardiac catheterization. Biomarker levels were determined and correlated with clinical data. IL-6 (11.75pg/ml, P<0.05) and sIL-6R (41,340pg/ml, P=0.05) were elevated in AMI compared with CAD and controls. At presentation, hsCRP was elevated in AMI patients (4.69mg/L) compared to controls (2.69mg/L, P<0.05); however, there was a significant decrease in hsCRP between AMI (4.69mg/L) and CAD patients (7.4mg/L, P<0.05). After 24h post-AMI hsCRP levels were increased compared to stable CAD (60.46mg/L, P<0.05) and were preceded by increased IL-6 at presentation. Soluble Gp130 (sGp130) showed no significant change between AMI, CAD, and control patients. However, sGp130 positively correlated with peak troponin in AMI (R=0.587, P<0.01), and negatively correlated with previous AMI (R=-0.382, P<0.05). Circulating monocyte mRNA expression isolated from selected AMI patients showed an increase in IL-6 mRNA (5.28-fold, P<0.01) and a decrease in both IL-6R (0.374-fold, P<0.01) and sGp130 mRNA (0.38-fold, P<0.01) as compared to CAD and controls. Results demonstrate that IL-6 and sIL-6R are associated with AMI and cardiac injury. These data support the hypothesis that trans-IL-6 receptor binding may alter intracellular signaling, and blocking of IL-6 receptor binding may be pathogenic in AMI. These data may be predictive of mechanism(s) by which plaques become unstable and rupture.

Changes in left ventricular longitudinal strain with anthracycline chemotherapy in adolescents precede subsequent decreased left ventricular ejection fraction.

BACKGROUND: Pediatric cancer survivors who have been exposed to anthracycline (ANT) chemotherapy are an ever increasing population at risk for premature cardiac disease. Studies have shown that ANT is associated with impaired left ventricular (LV) myocardial deformation, but this has not been shown to be associated with traditional echocardiographic measures of LV systolic dysfunction. The aim of this study was to test the hypothesis that changes in LV longitudinal peak systolic strain (LPSS) would correlate with parameters of LV systolic dysfunction. METHODS: This study included 19 prospectively enrolled pediatric patients receiving ANT (mean dose, 296 ± 103 mg/m(2)) and 19 controls matched for age, gender, and body surface area. For ANT patients, echocardiography was performed at baseline, mid, and final treatment points (0, 4, and 8 months). Standard echocardiographic parameters and two-dimensional speckle tracking-derived longitudinal strain parameters were obtained and compared with baseline measurements in controls. Associations between changes in LV global LPSS and standard echocardiographic indices were explored. RESULTS: Within the ANT group, the change in LV global LPSS showed a significant decrease compared with baseline at 4 months (8.7 ± 0.2%, P = .033) and 8 months (9.2 ± 0.3%, P = .015), while the percentage change in ejection fraction (EF) showed a statistically significant decrease at 8 months (4.3 ± 0.1%, P = .044). LV global LPSS was decreased in the ANT group compared with controls at 4 months (18.1 ± 2.5% vs 20.5 ± 1.5%, P = .011) and 8 months (18.1 ± 2.8%, P = .032). Segmental changes in mid and apical LV LPSS average were significantly correlated with change in EF (mid: r = -0.49, ß = -0.645, P = 0.039; apical: r = -0.48, ß = -0.4126, P = .046). CONCLUSIONS: In adolescents who receive ANT therapy, changes in two-dimensional LV global LPSS precede decreases in EF, and segmental changes in mid and apical LV LPSS suggest an increased likelihood that depressed LV EF will be observed later in follow-up. Two-dimensional speckle tracking-derived LV LPSS is potentially useful in the serial clinical monitoring of ANT cardiotoxicity.

Dynamic pulmonary artery obstruction causing right ventricular failure after cardiac transplantation in a patient with Mustard-Senning corrected d-transposition of the great arteries.

Patients with congenital d-transposition of the great arteries (d-TGA) undergoing palliative atrial baffle surgery in infancy often develop systemic ventricular failure in adulthood. If they undergo cardiac transplantation, they are prone to morphologic right ventricular (RV) failure secondary to severe pulmonary hypertension as a result of systemic ventricular failure. We report a case of a patient with d-TGA and biventricular ventricular failure requiring heart transplantation (HT) that developed RV failure postoperatively because of dynamic pulmonary artery (PA) obstruction at the anastomotic site of PA. Obstruction at the site of PA anastomosis due to torsion or redundancy of the donor or recipient PA is a rare but treatable cause of postoperative RV failure. In this case, rapid identification of the etiology of RV failure and implementation of corrective therapies before the development of end-organ dysfunction, resulted in complete RV recovery and normal allograft function. This case represents the first known report of dynamic PA anastomoticobstruction resulting in RV failure after HT that was corrected with pulmonary arterioplasty, and RV assist device resulting in complete recovery.

Rituximab-induced polymorphic ventricular tachycardia.

The anti-CD20 monoclonal antibody rituximab is an effective treatment for small lymphocytic lymphoma; however, it has been associated with infusion reactions, including cardiac arrhythmias. Severe cardiac arrhythmia is an adverse reaction that is related to rituximab chemotherapy, and more investigation is warranted into the adverse reactions of rituximab that involve cardiac conduction abnormalities. Herein, we report what we believe to be the 1st case of symptomatic polymorphic ventricular tachycardia to have occurred during an initial infusion of rituximab.