Prevalence, features and predictive factors of liver nodules in Fontan surgery patients: The VALDIG Fonliver prospective cohort.

BACKGROUND & AIMS: Fontan surgery is used to treat a variety of congenital heart malformations, and may lead to advanced chronic liver disease in the long-term. This study examines the prevalence, characteristics and predictors of liver nodules in patients following Fontan surgery. METHODS: This was a prospective, cross-sectional, observational study conducted at 8 European centres. Consecutive patients who had undergone Fontan surgery underwent blood tests, abdominal ultrasonography (US), transient elastography (Fibroscan®), echocardiography, haemodynamic assessments, and abdominal MRI/CT scan. The primary outcome measure was liver nodules detected in the MRI/CT scan. Predictors of liver nodules were identified by multivariate logistic regression. RESULTS: One hundred and fifty-two patients were enrolled (mean age 27.3 years). The mean time elapsed from surgery to inclusion was 18.3 years. Liver nodule prevalences were 29.6% (95% CI 23-37%) on US and 47.7% (95% CI 39-56%) on MRI/CT. Nodules were usually hyperechoic (76.5%), round-shaped (>80%), hyperenhancing in the arterial phase (92%) and located in the liver periphery (75%). The sensitivity and specificity of US were 50% (95% CI 38-62%) and 85.3% (95% CI 75-92%), respectively. Inter-imaging test agreement was low (adjusted kappa: 0.34). In the multivariate analysis, time since surgery >10 years was the single independent predictor of liver nodules (odds ratio 4.18; p = 0.040). Hepatocellular carcinoma was histologically diagnosed in 2 of the 8 patients with hypervascular liver nodules displaying washout. CONCLUSION: While liver nodules are frequent in Fontan patients, they may go unnoticed in US. Liver nodules are usually hyperechoic, hypervascular and predominantly peripheral. This population is at risk of hepatocellular carcinoma, the diagnosis of which requires confirmatory biopsy. LAY SUMMARY: Fontan surgery is the standard of care for many patients with univentricular congenital cardiopathies. Recent advances have improved the survival of Fontan patients, and nowadays most of them reach adulthood. In this setting, Fontan-associated liver disease (FALD) is increasingly recognised, and has become a significant prognostic factor. Liver nodules are considered a component of FALD yet their prevalence, imaging features and predictors have hardly been evaluated. In this study, we observed that liver nodules are frequent, typically hyperechoic, hypervascular and predominantly peripheral in patients with FALD. This population is at risk of hepatocellular carcinoma, the diagnosis of which must be confirmed by biopsy.

Decreased clinical performance in TGA-ASO patients after RVOT interventions; a multicenter European collaboration.

BACKGROUND: In patients with transposition of the great arteries and an arterial switch operation (TGA-ASO) right ventricular outflow tract (RVOT) obstruction is a common complication requiring one or more RVOT interventions. OBJECTIVES: We aimed to assess cardiopulmonary exercise capacity and right ventricular function in patients stratified for type of RVOT intervention. METHODS: TGA-ASO patients (≥16 years) were stratified by type of RVOT intervention. The following outcome parameters were included: predicted (%) peak oxygen uptake (peak VO2), tricuspid annular plane systolic excursion (TAPSE), tricuspid Lateral Annular Systolic Velocity (TV S'), right ventricle (RV)-arterial coupling (defined as TAPSE/RV systolic pressure ratio), and N-terminal proBNP (NT-proBNP). RESULTS: 447 TGA patients with a mean age of 25.0 (interquartile range (IQR) 21-29) years were included. Patients without previous RVOT intervention (n = 338, 76%) had a significantly higher predicted peak VO2 (78.0 ± 17.4%) compared to patients with single approach catheter-based RVOT intervention (73.7 ± 12.7%), single approach surgical RVOT intervention (73.8 ± 28.1%), and patients with multiple approach RVOT intervention (66.2 ± 14.0%, p = 0.021). RV-arterial coupling was found to be significantly lower in patients with prior catheter-based and/or surgical RVOT intervention compared to patients without any RVOT intervention (p = 0.029). CONCLUSIONS: TGA patients after a successful arterial switch repair have a decreased exercise capacity. A considerable amount of TGA patients with either catheter or surgical RVOT intervention perform significantly worse compared to patients without RVOT interventions.

Combined Heart and Liver Transplantation for Uhl's Anomaly: A Case Report.

BACKGROUND: Uhl's anomaly is an extremely rare congenital heart defect characterized by absence of the right ventricle myocardium and preserved left ventricular myocardium. Although the disease has a poor prognosis and is generally fatal in the perinatal period, some patients may reach adulthood. METHODS: We describe a case of Uhl's anomaly complicated with heart failure and decompensated cardiac cirrhosis in a 42-year-old man treated by combined heart-liver transplant. RESULTS: The patient underwent heart transplant using the bicaval technique followed by subsequent liver transplant with the piggyback technique without venovenous bypass. Total ischemia time was 108 minutes for the heart and 360 and 25 minutes of cold and warm ischemia, respectively, for the liver. No intraoperative complications occurred. The patient was discharged without severe complications on postoperative day 22. Pathologic examination of the organs reported advanced cirrhosis of the liver and severe dilated myocardiopathy of right ventricle with absence of myocardium and a normal left ventricle. Twenty-seven months after the transplant the patient has been free from hospital admissions, with normal function of both transplanted organs. CONCLUSIONS: We report the first successful combined heart-liver transplant for Uhl's anomaly indication in an adult patient. Despite of the insufficient knowledge of natural history of this exceptional disease, we successfully apply the management principles of other end-stage right heart disorders complicated with liver failure.

Correction: Lung and heart-lung transplantation in pulmonary arterial hypertension.

[This corrects the article DOI: 10.1371/journal.pone.0187811.].

Atrial flutter in a patient with atrial septal defect and anomalous venous drainage: unusual approach for ablation.

Atrial flutter ablation in CHD (Congenital Heart Disease) patients is a challenging procedure because of the possibility of multiple circuits. Electroanatomical mapping and pacing maneuvers are crucial to determine critical isthmus. Moreover, vascular abnormalities and residual cardiac defects need to be known before the ablation to decide the better strategy for ablation.

Lung and heart-lung transplantation in pulmonary arterial hypertension.

BACKGROUND: Real use of lung (LT) and heart-lung (HLT) transplantation in pulmonary arterial hypertension (PAH) is unknown. The objectives were to describe the indication of these procedures on PAH treatment in a national cohort of PAH patients, and to analyze the potential improvement of its indication in severe patients. METHODS: Eligibility for LT/HLT was assessed for each deceased patient. Incident patients from REHAP diagnosed between January 2007 and March 2015 and considered eligible for LT/HLT were grouped as follows: those who finally underwent transplantation (LTP) and those who died (D-Non-LT). FINDINGS: Of 1391 patients included in REHAP, 36 (3%) were LTP and 375 (27%) died. Among those who died, 36 (3%) were D-Non-LT. LTP and D-Non-LT were equal in terms of age, gender, and clinical status. Ten percent of those who died were functional class I-II. Patients functional class IV were less likely to undergo LT (8.3% LTP vs. 30.6% D-Non-LT, p = 0.017). Patients with idiopathic and drug/toxin-associated PAH were more likely to undergo LT (44.4% LTP vs. 16.7% D-Non-LT, p = 0.011). CONCLUSIONS: The present results show that the use of LT/HLT could double for this indication. Relevant mortality in early functional class reflects the difficulties in establishing the risk of death in PAH.

Mechanical valves in the pulmonary position: An international retrospective analysis.

OBJECTIVE: Life expectancy of patients with congenital heart disease has improved over the past decades, increasing the need for a durable pulmonary prosthetic valve. Biological valves in various forms have become the valve of choice for pulmonary valve replacement (PVR), but structural valve deterioration is unavoidable in the long term. Use of a mechanical valve could be an alternative, but data on long-term outcomes are sparse. METHODS: We retrospectively collected and analyzed data on 364 patients with mechanical valves implanted in the pulmonary position between 1965 and 2014. The data originate from medical centers in Barcelona (Spain), Graz (Austria), Groningen (the Netherlands), Munich (Germany), Rochester (United States), Seoul (Republic of Korea), and Tehran (Iran). RESULTS: Median follow-up duration was 4.26 years (range, 0-27 years), mean age at implantation was 27.16 ± 12.2 years. Tetralogy of Fallot was the most common primary cardiac diagnosis, with a subgroup of 69.8%. Freedom from valvular thrombosis was 91% (95% confidence interval [CI], 87%-94%) at 5 years and 86% (95% CI, 81%-91%) at 10 years post-PVR. With a success rate up to 88%, thrombolysis was a successful therapy. Freedom from reoperation was 97% (95% CI, 94%-99%) at 5 years post-PVR and 91% (95% CI, 85%-95%) at 10 years. CONCLUSIONS: Mechanical PVR is associated with a limited risk of valvular thrombosis. Thrombolysis was an effective treatment in the majority.

Predictors of obstetric complications in women with heart disease.

OBJECTIVES: The objective of this study is to evaluate obstetric outcomes in women with heart disease and determine whether current multidisciplinary management approaches adversely affect the mother, the neonate, or both. Also to compare the accuracy of several risk scores (RS) including the modified World Health Organization classification (mWHO) and CARPREG to predict obstetric and neonatal complications and to study the addition value of Uteroplacental-Doppler flow (UDF) parameters to predict obstetric complications. METHODS: A prospective cohort study examined outcomes in women with heart disease (HD), the majority of whom had corrective surgery and delivered between January 2007 and March 2012. RESULTS: One hundred and seventy-four patients with 179 pregnancies were included in the study. Obstetric complications, including premature labor, arose in 87 patients (48.6%). Neonatal complications were observed in 11 cases (7%). On multivariate analysis, maternal heart disease was predictive of adverse perinatal events (46 cases, 25.7%) and mode of delivery (Thierry's spatula) of third- or fourth-degree perineal tears (six cases, 3.2%). mWHO classification predicted obstetric complications (p = 0.0001) better than the CARPREG study. Impaired UDF (uterine artery pulsatility index-20 weeks and umbilical artery pulsatility index-32 weeks in HD versus healthy women: 20w 1.12 versus 1.34, p = 0.005; 32w 0.87 versus 1.09, p = 0.008) was associated with adverse obstetric and offspring outcome in the group of HD pregnant women. CONCLUSIONS: Nearly 50% of pregnancies were associated with an adverse obstetric outcome, particularly IUGR. mWHO was better at predicting obstetric and neonatal complications that CARPREG in all categories. Furthermore, compromised UDF combined with mWHO improved the prediction of obstetric and offspring complications in this population.

[Use of oral anticoagulants in patients discharged with atrial fibrillation in 2000]. / Utilización de anticoagulantes orales en pacientes con fibrilación auricular al alta hospitalaria en el año 2000.

INTRODUCTION AND OBJECTIVES: Although there is consensus about the use of oral anticoagulants to prevent thrombi and embolisms in most patients with atrial fibrillation, this treatment is underused in actual practice. Our objective was to determine and analyze the use of acenocoumarol in patients diagnosed as having atrial fibrillation at discharge. PATIENTS AND METHOD: Between January and July 2000, we retrospectively studied 501 consecutive patients with a diagnosis of atrial fibrillation. We recorded whether they were discharged with or without oral anticoagulation treatment. RESULTS: We identified 482 patients with at least one associated thromboembolic risk factor, who comprised the study population. Mean age was 79.3 years, and 33.3% of the patients were men. Forty-six percent were discharged with acenocoumarol, and 36.3% with platelet antiaggregants. Twenty-three percent had a known contraindication for acenoroumarol. Nearly 62% of the patients without contraindications for anticoagulation received treatment with acenocoumarol. Multivariate analysis showed that rheumatic mitral valve disease, previous stroke or thromboembolism and dilated left atrium were associated with a higher probability of receiving anticoagulant treatment. Age over 75 years was associated with a lower likelihood of receiving acenocoumarol. CONCLUSIONS: Oral anticoagulation was given in an inadequate proportion of patients who were discharged from a secondary-level hospital with atrial fibrillation and no contraindications. Rheumatic mitral valve disease, previous stroke or thromboembolism, and dilated left atrium were associated with a higher probability of anticoagulant treatment. Age over 75 years was related with less frequent use of this therapy.

[Identification of factors responsible for oral over-anticoagulation in outpatients with heart disease]. / Identificación de factores responsables de anticoaguación oral excesiva en pacientes ambulatorios con cardiopatía.

BACKGROUND: Few studies have attempted to investigate the clinical course or identify factors responsible for excessive anticoagulation in patients with heart disease. OBJECTIVES: To determine the incidence of excessive anticoagulation in outpatients with heart disease treated with acenocoumarol, analyze the factors related with over-anticoagulation, and identify bleeding complications. PATIENTS AND METHOD: This 7-month prospective observational study included consecutive outpatients anticoagulated with acenocoumarol. They were seen in an anticoagulation unit. The high INR group of 55 over-anticoagulated patients had at least one test with INR > 5. The control group of 49 patients had INR results strictly within therapeutic range. RESULTS: A total of 3,683 INR determinations were made in 512 patients. Seventy-seven tests had an INR > 5 (a 2% overall incidence of high-INR). In the group of 55 INR < 5 patients, 31% had more than one INR determination > 5 during follow-up. Multivariate analysis identified four variables as independent predictors of over-anticoagulation: artificial heart valve, poor treatment compliance, addition of potentially interactive new drugs, and illness in the last month. The high-INR group patients had more bleeding episodes (21.8 vs 4.08%; p = 0.008), one of which was major. CONCLUSION: The incidence of excessive oral anticoagulation in our outpatient population was similar to that reported in other studies. Patients with INR > 5 had more total bleeding complications, mostly minor. It is recommended to proceed carefully with oral anticoagulant therapy in patients with an artificial heart valve, suspected poor treatment compliance, addition of potentially interactive new drugs, and illness in the last month.

Eplerenone in systemic right ventricle: double blind randomized clinical trial. The evedes study.

BACKGROUND: There is no proven pharmacological strategy for the treatment of the failing systemic right ventricle (SRV) but myocardial fibrosis may play a role in its pathophysiology. METHODS: We designed a double-blind, placebo-controlled clinical trial to assess the effects of eplerenone 50mg during 12 months on cardiac magnetic resonance parameters (SRV mass and ejection fraction) and neurohormonal and collagen turnover biomarker (CTB) levels. RESULTS: Twenty six patients with atrial switch repair for transposition of the great arteries were randomized to eplerenone (n=14) or placebo (n=12) and 14 healthy volunteers served as controls for comparison of baseline neurohormones and CTB levels. The study population showed a good baseline profile in terms of SRV mass (57.4 ± 17 g/m(2)) and ejection fraction (54.9 ± 7.5%). However, levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), C terminal propeptide of type I procollagen (CICP) and C-terminal Telopeptide of type I Collagen (ICTP) were significantly elevated when compared to healthy controls. After one year of treatment, a trend toward reduction of CICP, N-terminal pro-Matrix Metalloproteinase 1 (NT-proMMP1), Tissue Inhibitor of Metalloproteinases 1 (TIMP1) and galectin 3 levels and a lower increase in ICTP in patients under eplerenone was observed. The reduction of SRV mass and the improvement of SRV function with eplerenone were not conclusive. CONCLUSIONS: Patients with SRV treated with eplerenone showed an improvement of an altered baseline CTB profile suggesting that reduction of myocardial fibrosis might be a therapeutic target in these patients.

The left heart after pulmonary valve replacement in adults late after tetralogy of Fallot repair.

BACKGROUND: Adverse ventricular-ventricular interactions have been recognized in those with repaired tetralogy of Fallot (TOF) and severe pulmonary regurgitation. OBJECTIVE: We aimed to examine the impact of pulmonary valve replacement (PVR) on the left heart late after TOF repair. METHODS AND RESULTS: Left ventricular (LV) volumes and ejection fractions (EF) were analyzed in adults with severe pulmonary regurgitation after TOF repair with cardiac magnetic resonance imaging (CMR) before and after PVR. Thirty-nine patients (median age 33[20-65] years) were reviewed. Post-PVR, LVEF improved significantly in the entire cohort (50 ± 9%→54 ± 7%, p<0.001) and in those with moderately impaired (defined as LVEF ≤ 45%) preoperative LVEF (38 ± 5%→47 ± 6%, p<0.0001), but was not statistically different in those with relatively preserved (defined as LVEF >45%) preoperative LVEF. By multivariate linear regression analysis to evaluate independent CMR predictors of improved LVEF post-PVR for the entire cohort, the only CMR variable to emerge was preoperative LVEF (p=0.012, regression coefficient -0.54, SE 0.13). Whereas PVR resulted in increased LV filling in patients with relatively preserved preoperative LVEF reflected by an increase in LV end-diastolic volumes (77 ± 10→82 ± 16 mL/m(2), p=0.05), LV end-systolic volumes decreased after PVR in patients with impaired preoperative LVEF (65 ± 12→54 ± 10 mL/m(2), p=0.001) but LV end-diastolic volumes were not significantly changed. CONCLUSION: When LVEF is decreased after TOF repair, PVR appears to have a salutary effect on postoperative LVEF, thereby supporting the concept of recovery of adverse right-left heart interactions. Mechanisms of left heart improvement post-PVR differ depending on degree of preoperative LV systolic dysfunction.

Long term outcome of mechanical valve prosthesis in the pulmonary position.

OBJECTIVES: Assessment of the long term outcome of mechanical valve prosthesis at pulmonary position in a population of grown-up congenital heart disease patients from a tertiary referral center. METHODS: From 1977 to 2007, 22 consecutive patients underwent a total of 25 pulmonary valve replacements with mechanical prosthesis. The most frequent underlying cardiac condition was tetralogy of Fallot (n=16, 64%) and the mean age at the time of pulmonary valve replacement was 32 ± 11 years (range 14-50 years). RESULTS: The postoperative mortality rate was 4% (n=1) with no late deaths documented after a mean follow-up of 7.6 ± 7.6 years (range 0.29-24 years). No major bleeding episodes occurred. Three patients presented with valve thrombosis in the setting of long term anticoagulation withdrawal and required valve re-replacement. Two of these patients, both with poor right ventricular function and overt clinical signs of right heart failure at the time of valve re-replacement, experienced further episodes of thrombosis despite correct anticoagulation. All episodes resolved with thrombolysis. After addition of antiplatelet treatment in one case and anticoagulation self-control, in the other, no further thrombosis has been documented. CONCLUSIONS: Mechanical valve prosthesis may be an alternative to tissue valve prosthesis in patients with congenital heart disease requiring pulmonary valve replacement. Optimal anticoagulation is crucial and additional antiplatelet treatment should be considered. Our data also suggest that patients with severe right ventricular dysfunction and congestive heart failure might be at particular risk for valve thrombosis.

Pulmonary valve replacement in repaired tetralogy of Fallot: determinants of early postoperative adverse outcomes.

OBJECTIVE: We sought to examine the frequency of early postoperative complications and preoperative predictors of prolonged hospitalization in adults with repaired tetralogy of Fallot undergoing pulmonary valve replacement. METHODS: This was a retrospective study of consecutive adult patients undergoing surgical intervention between 1995 and 2006. A multivariate logistic regression model was used to identify determinants of prolonged hospitalization. RESULTS: One hundred sixteen patients (mean age, 36 +/- 11 years) underwent 118 pulmonary valve replacements. Most (95%) operations included additional procedures, such as pulmonary artery/outflow tract reconstruction or tricuspid valve annuloplasty. The early postoperative mortality (<30 days) was 2.5%. The majority of the patients (60%) had no postoperative complications. The postoperative adverse events included postoperative arrhythmias (19%), respiratory complications (13%), reoperation during admission (13%), renal dysfunction (13%), and myocardial infarction (3%). Postoperative adverse events were associated with prolonged hospitalization (14 +/- 12 vs 7 +/- 3 days, P = .001). In the multivariate analysis age at reoperation of greater than 45 years (odds ratio, 6.1; 95% confidence interval, 1.6-23.6; P = .009), the number of previous sternotomies (odds ratio, 3.8; 95% confidence interval, 1.4-10; P = .007), and the need for urgent surgical intervention (odds ratio, 5.7; 95% confidence interval, 1.1-27.8; P = .03) were predictors of prolonged hospitalization. CONCLUSION: Pulmonary valve replacement in adults with repaired tetralogy of Fallot has a low mortality risk. The most common early postoperative complications are arrhythmias and respiratory and renal complications. Although most early postoperative complications do not result in long-term sequelae, they are associated with prolonged hospitalization. Patients undergoing urgent interventions, older patients, and those with multiple previous sternotomies are at the highest risk for prolonged hospitalization.

Cardiac alterations in cirrhosis: reversibility after liver transplantation.

BACKGROUND/AIMS: Liver cirrhosis induces cardiac alterations. We aimed to define these alterations and assess their reversibility after transplantation. METHODS: Cirrhotic patients (n = 40) and controls (n = 15) underwent echocardiography and stress ventriculography. Fifteen cirrhotics were reevaluated 6-12 months after transplantation. RESULTS: Cirrhotics had higher left ventricular wall thickness (9.6+/-1.2 vs. 8.8+/-1.2 mm; P < 0.05) and ejection fraction (73+/-6 vs. 65+/-4%, P < 0.001) than controls. Basal diastolic function was similar. During stress, cirrhotics presented lower increases of heart rate, left ventricular ejection fraction, stroke volume and cardiac index (P < 0.05 for all), and diastolic dysfunction with lower ventricular peak filling rate (P = 0.001). Exercise capacity was reduced (48+/-21 vs. 76+/-24 W; P < 0.001). Ascitic patients exhibited more diastolic dysfunction at rest and during stress compared to non-ascitic patients. Liver transplantation caused regression of ventricular wall thickness (10.2+/-1.3 vs. 9.5+/-1.2 mm; P < 0.05), improvement of diastolic function, and normalization of systolic response and exercise capacity during stress (significant increases in heart rate, ventricular ejection fraction, stroke volume and cardiac index; P < 0.05 for all). CONCLUSIONS: Cardiac alterations in cirrhosis present with mild increases in ventricular wall thickness, diastolic dysfunction that worsens with ascites and physical stress, and abnormal systolic response to stress limiting exercise capacity. Liver transplantation reverses these alterations.