Incidence, Predictors, and Mortality in Patients With Liver Cancer After Fontan Operation

Background Liver cancer (LC) is a serious late complication after the Fontan operation. However, the incidence, predictors, and prognosis remain unknown. The purpose of our study was to determine these clinical characteristics. Methods and Results We assessed liver function in 339 consecutive patients who had undergone the Fontan procedure from 2005 to 2019. LC was histologically diagnosed in 10 patients after a median period of 2.9 years (range: 0.3–13.8; median age: 29.9 years [range: 14.4–41.5 years]; overall median post–Fontan procedure follow‐up: 25.6 years [range: 13–32.1 years]), and the annual incidence was 0.89%. Over the entire post‐Fontan follow‐up period, the annual incidences of new‐onset LC in the second, third, and fourth decades were 0.14%, 0.43%, and 8.83%, respectively. The patients with LC had longer follow‐up periods, higher levels of AFP (α‐fetoprotein), and higher values of liver fibrosis indices ( P <0.01–0.0001). Moreover, all indices were predictive of new‐onset LC ( P <0.01–0.0001). The LC treatments were surgical resection (n=3), transarterial chemoembolization (n=3), radiofrequency ablation (n=2), and hospice care (n=2). During a median follow‐up of 9.4 months, 4 patients died; the survival rate at 1 year was 60%, and it was better among asymptomatic patients ( P <0.01). Conclusions The LC incidence rapidly increased ≥30 years after the Fontan procedure, and liver fibrosis indices and AFP were predictive of new‐onset LC. These LC‐predictive markers should be monitored closely and mandatorily for early LC detection and better prognosis.

Download Full-text

A prospective follow-up study of the relationship between high-sensitivity C-reactive protein and primary liver cancer

BMC Cancer ◽

10.1186/s12885-020-07665-9 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Sarah Tan Siyin ◽

Tong Liu ◽

Wenqiang Li ◽

Nan Yao ◽

Guoshuai Xu ◽

...

Keyword(s):

Liver Cancer ◽

Regression Models ◽

Primary Liver Cancer ◽

High Sensitivity ◽

C Reactive Protein ◽

Reactive Protein ◽

Hs Crp ◽

The Relationship ◽

New Onset

Abstract Background Competing risk method has not been used in a large-scale prospective study to investigate whether increased levels of high-sensitivity C-reactive protein (hs-CRP) elevate the risk of primary liver cancer (PLC). Our study aims to prospectively investigate the relationship between hs-CRP and new-onset PLC. Methods and results Ninety-five thousand seven hundred fifty-nine participants without the diagnosis of PLC, and who had their demographic characteristics and biochemical parameters recorded, were analyzed from the Kailuan Cohort study. Cox proportional hazards regression models and competing risk regression models were used to evaluate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) of PLC. During a median follow-up of 11.07 years, 357 incidental PLC cases were identified over a total of 1,035,039 person-years. The multivariable HRs (95%CI) for the association of hs-CRP of 1–3 mg/L group and hs-CRP>3 mg/L with PLC were 1.07(0.82 ~ 1.38), 1.51(1.15 ~ 1.98) in a Cox proportional hazard regression analysis adjusted for other potential confounders. In the cause-specific hazard model, the multivariable HRs (95%CI) for the association of hs-CRP of 1–3 mg/L group and hs-CRP>3 mg/L with PLC were 1.06(0.81 ~ 1.40), 1.50(1.14 ~ 1.99). Similar results were also observed in the sub-distribution hazard function model with corresponding multivariate HRs (95%CI) of 1.05(0.80 ~ 1.40), 1.49(1.13 ~ 1.98) in hs-CRP of 1–3 mg/L group and hs-CRP>3 mg/L group, respectively. Conclusions This prospective study found a significant association of higher levels of hs-CRP with new-onset PLC. The main clinical implications would be an increased awareness of hs-CRP and its correlation to the risk of PLC. This study should be a steppingstone to further research on chronic inflammation and PLC. Trial registration Registration number:ChiCTR–TNRC–11001489.

Download Full-text

Long-term outcome after atrioventricular valve surgery following modified Fontan operation

Cardiology in the Young ◽

10.1017/s1047951110001538 ◽

2010 ◽

Vol 21 (1) ◽

pp. 83-88 ◽

Cited By ~ 19

Author(s):

Shaji C. Menon ◽

Joseph A. Dearani ◽

Frank Cetta

Keyword(s):

Ventricular Function ◽

Fontan Procedure ◽

Fontan Operation ◽

Valve Surgery ◽

Atrioventricular Valve ◽

Term Outcome ◽

Protein Losing Enteropathy ◽

Long Term Outcome

AbstractObjectiveThe objective of this study was to evaluate the early and late results of atrioventricular valve surgery after Fontan operation.BackgroundAtrioventricular valve regurgitation is a known perioperative risk factor for Fontan operation. There are limited data on the outcomes of late atrioventricular valve surgery following Fontan operation.MethodsPatients who underwent atrioventricular valve surgery following Fontan procedure were identified from the Mayo Clinic Fontan database. Medical records were reviewed for pre-operative, operative, and post-operative clinical and haemodynamic data. All patients not known to be deceased were sent health status questionnaires.ResultsA total of 61 patients (28 females) underwent atrioventricular valve surgery following Fontan procedure. The median age at atrioventricular valve surgery was 14 years. The median duration between Fontan and atrioventricular valve surgery was 4.7 years. Median follow-up was 9 years. There were a total of 32 (52%) deaths with 8 (13%) within 30 days of surgery. The 5-, 10-, and 15-year survival rates were 67%, 57%, and 45%, respectively. On follow-up, 44 of 61 (72%) had arrhythmias, 21 of 29 (72%) were symptomatic, and 12 of 61 (20%) developed protein-losing enteropathy. On multivariate analysis, reduced ventricular function and development of protein-losing enteropathy were associated with decreased survival.ConclusionAtrioventricular valve surgery after Fontan procedure is associated with substantial late morbidity and mortality. Atrioventricular valve surgery in this cohort of patients portends poor long-term outcome and is associated with a high incidence of protein-losing enteropathy. Reduced ventricular function and development of protein-losing enteropathy were associated with decreased survival.

Download Full-text

Noninvasive Assessment of Liver Stiffness in Patients Undergoing the Fontan Procedure

World Journal for Pediatric and Congenital Heart Surgery ◽

10.1177/2150135120935418 ◽

2020 ◽

Vol 11 (5) ◽

pp. 572-577 ◽

Cited By ~ 1

Author(s):

Sachin Talwar ◽

Vasubabu Gudala ◽

Raja Joshi ◽

DM Shalimar ◽

Kumble Seetharama Madhusudhan ◽

...

Keyword(s):

Liver Injury ◽

Transient Elastography ◽

Early Recognition ◽

Fontan Procedure ◽

Fontan Operation ◽

Liver Stiffness ◽

Shear Wave Elastography ◽

Noninvasive Methods ◽

Over Time

Background: Hepatic derangements and liver injury following the Fontan operation (FO) may progress in some cases to hepatic fibrosis (HF) and cirrhosis. The respective roles of transient elastography (TE) or FibroScan, shear wave elastography (SWE), and aspartate transaminase to platelet ratio index (APRI) in assessing liver stiffness (LS) and possible liver injury in these patients are unclear. Methods: Thirty-nine patients (31 males), mean age 11.8 ± 5.7 years, median 11 years (interquartile range: 7-14.7 years), undergoing the FO between November 2017 and December 2018 were included. Liver stiffness and HF assessment was done with TE, SWE, and APRI in the preoperative period and postoperatively at 3-, 6-, and 12-month interval. Results: The LS values increased over time (postoperative values at 3, 6, and 12 months) as compared to preoperative values by both FibroScan and SWE. The change in liver stiffness measurement (LSM) was statistically significant: LSM0 to LSM3 ( P ≤ .0001), LSM0 to LSM6 ( P ≤ .0001), and LSM0 to LSM12 ( P = .001). Similarly, significant changes were observed on SWE: SWE0 to SWE3 ( P ≤ .0001), SWE0 to SWE6 ( P ≤ .0001), and SWE0 to SWE12 ( P = .001). There was no significant change in the APRI values over time. Conclusion: Noninvasive methods such as FibroScan and SWE may be of use to assess LS in follow-up of patients undergoing the FO for early recognition of hepatic changes.

Download Full-text

Outcomes of the Non-fenestrated Fontan Procedure at High Altitude

World Journal for Pediatric and Congenital Heart Surgery ◽

10.1177/2150135119862607 ◽

2019 ◽

Vol 10 (5) ◽

pp. 590-596 ◽

Cited By ~ 1

Author(s):

Alexis Palacios-Macedo ◽

Héctor Díliz-Nava ◽

Orlando Tamariz-Cruz ◽

Luis García-Benítez ◽

Fabiola Pérez-Juárez ◽

...

Keyword(s):

Risk Factor ◽

Oxygen Saturation ◽

High Altitude ◽

Fontan Procedure ◽

Fontan Operation ◽

Hospital Death ◽

Medium Term ◽

Drainage Time ◽

Extracardiac Fontan

Background: Although high altitude has been considered a risk factor for the Fontan operation, and an indication for fenestration, there is a paucity of data to support its routine use. Fenestration, with its necessary right to left induced shunt, together with the lower partial pressure of oxygen found with progressive altitude, can significantly decrease hemoglobin oxygen saturation, and therefore, it would be desirable to avoid it. Objective: To analyze immediate and medium-term results of the non-fenestrated, extracardiac, Fontan procedure at high altitude. Methods: Retrospective analysis of data from consecutive patients who underwent non-fenestrated, extracardiac, Fontan procedure at two institutions located in Mexico City at 2,312 m (7,585 ft) and 2,691 m (8,828 ft) above sea level. High altitude was not considered a risk factor. Results: Thirty-nine patients were included, with a mean age of 6.7 years. Mean preoperative indexed pulmonary vascular resistance was 1.7 Wood units. Seventy-nine percent of the patients extubated in the operating room. There was one in-hospital death (2.56%) and one at follow-up. Median chest tube drainage time was 6.5 and 6 days for the right and left pleural spaces. Median oxygen saturation at discharge was 90%. At a median follow-up of six months, all survivors, except one, had good tolerance to daily life activities. Conclusions: The present study shows good short- and medium-term results for the non-fenestrated, extracardiac, Fontan operation at altitudes between 2,300 and 2,700 m and might favor this strategy over fenestration to improve postoperative oxygen saturation. Further studies to examine the long-term outcomes of this approach need to be considered.

Download Full-text

Risk of Liver Cirrhosis and Hepatocellular Carcinoma after Fontan Operation: A Need for Surveillance

Cancers ◽

10.3390/cancers12071805 ◽

2020 ◽

Vol 12 (7) ◽

pp. 1805

Author(s):

Jun Sik Yoon ◽

Dong Ho Lee ◽

Eun Ju Cho ◽

Mi Kyoung Song ◽

Young Hun Choi ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cirrhosis ◽

Cumulative Incidence ◽

Rare Complication ◽

Fontan Procedure ◽

Fontan Operation ◽

Late Complication ◽

Elevated Serum ◽

Arterial Phase ◽

Portal Venous Phase

Liver cirrhosis and hepatocellular carcinoma (HCC) are serious late complications that can occur after the Fontan procedure. This study aimed to investigate the cumulative incidence of cirrhosis and HCC and to identify specific features distinguishing HCC from benign arterial-phase hyperenhancing (APHE) nodules that developed after the Fontan operation. We retrospectively enrolled 313 post-Fontan patients who had been followed for more than 5 years and had undergone ultrasound or computed tomography (CT) of the liver between January 2000 and August 2018. Cirrhosis was diagnosed radiologically. The estimated cumulative incidence rates of cirrhosis at 5, 10, 20, and 30 years after the Fontan operation were 1.3%, 9.2%, 56.6%, and 97.9%, respectively. Multiphasic CT revealed that 18 patients had APHE nodules that were ≥1 cm in size and showed washout in the portal venous phase (PVP)/delayed phase, which met current noninvasive HCC diagnosis criteria. Among them, only seven patients (38.9%, 7/18) were diagnosed with HCC. After cirrhosis developed, the annual incidence of HCC was 1.04%. The appearance of washout in the PVP (p = 0.006), long time elapsed since the initial Fontan operation (p = 0.04), large nodule size (p = 0.03), and elevated serum α-fetoprotein (AFP) level (p < 0.001) were significantly associated with HCC. In conclusion, cirrhosis is a frequent late complication after Fontan operation, especially after 10 years, and HCC is not a rare complication after cirrhosis development. Diagnosis of HCC should not be based solely on the current imaging criteria, and washout on PVP and clinical features might be helpful to differentiate HCC nodules from benign APHE nodules.

Download Full-text

Systemic ventricle morphology impact on ten-year survival after Fontan surgery

Asian Cardiovascular and Thoracic Annals ◽

10.1177/0218492318810647 ◽

2018 ◽

Vol 26 (9) ◽

pp. 677-684 ◽

Cited By ~ 1

Author(s):

Mira Fauziah ◽

Oktavia Lilyasari ◽

Lies Dina Liastuti ◽

Budi Rahmat

Keyword(s):

Survival Rate ◽

Fontan Procedure ◽

Fontan Operation ◽

Survival Rates ◽

Univentricular Heart ◽

Thromboembolic Events ◽

Term Survival ◽

Systemic Ventricle ◽

The Impact

Background The Fontan procedure has been applied in many patients with single-ventricle physiology, with quite low mortality rates all over the world, and a 8.6%–9.1% rate in Indonesia. Structural and characteristic differences in the morphologically left and right ventricles influence the role of the systemic ventricle in the functionally univentricular heart and impact on postoperative outcomes. Mid- and long-term survival based on systemic ventricle morphology remains controversial. This study aimed to investigate the impact of systemic ventricle morphology on ten-year survival after the Fontan procedure. Methods The 162 patients who underwent a Fontan operation at our institution between 2008 and February 2018 and survived to discharge were reviewed and followed up until March 2018. Data were extracted from the registry and pediatric surgical conferences, medical records, surgery reports, echocardiography and catheterization reports, and follow-up to the end of the study period. Median follow-up was 26.5 months (range 10.75–54 months). Results The patients were divided into 2 groups based on systemic ventricle morphology. Seventy-four patients were included in the left morphology group and 88 in the right morphology group. There was no difference in 10-year survival rates between the two type of systemic ventricle morphology. Postoperative thromboembolic events influenced the 10-year survival rate after the Fontan procedure (hazard ratio 4.84, 95% confidence interval: 1.26–18.55, p = 0.021). Conclusion Systemic ventricle morphology was not associated with the 10-year survival rate after the Fontan procedure. Postoperative thromboembolic events accounted for a 4.84-times higher mortality risk after the Fontan procedure.

Download Full-text

Biomarker profiling for risk of future heart failure (HFpEF) development

Journal of Translational Medicine ◽

10.1186/s12967-021-02735-3 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Chris J. Watson ◽

Joe Gallagher ◽

Mark Wilkinson ◽

Adam Russell-Hallinan ◽

Isaac Tea ◽

...

Keyword(s):

Heart Failure ◽

Relative Risk ◽

Future Development ◽

Interleukin 6 ◽

Disease Risk ◽

Cardiovascular Disease Risk ◽

Asymptomatic Patients ◽

Galectin 3 ◽

New Onset

Abstract Background The purpose of this study was to investigate the utility of BNP, hsTroponin-I, interleukin-6, sST2, and galectin-3 in predicting the future development of new onset heart failure with preserved ejection fraction (HFpEF) in asymptomatic patients at-risk for HF. Methods This is a retrospective analysis of the longitudinal STOP-HF study of thirty patients who developed HFpEF matched to a cohort that did not develop HFpEF (n = 60) over a similar time period. Biomarker candidates were quantified at two time points prior to initial HFpEF diagnosis. Results HsTroponin-I and BNP at baseline and follow-up were statistically significant predictors of future new onset HFpEF, as was galectin-3 at follow-up and concentration change over time. Interleukin-6 and sST2 were not predictive of future development of new onset HFpEF in this study. Unadjusted biomarker combinations of hsTroponin-I, BNP, and galectin-3 could significantly predict future HFpEF using both baseline (AUC 0.82 [0.73,0.92]) and follow-up data (AUC 0.86 [0.79,0.94]). A relative-risk matrix was developed to categorize the relative-risk of new onset of HFpEF based on biomarker threshold levels. Conclusion We provided evidence for the utility of BNP, hsTroponin-I, and Galectin-3 in the prediction of future HFpEF in asymptomatic event-free populations with cardiovascular disease risk factors.

Download Full-text

Long-term Results of Additional Pulmonary Blood Flow With Bidirectional Cavopulmonary Shunt

10.21203/rs.3.rs-31559/v1 ◽

2020 ◽

Author(s):

Ryosuke Kowatari ◽

Yasuyuki Suzuki ◽

Kazuyuki Daitoku ◽

Ikuo Fukuda

Keyword(s):

Blood Flow ◽

Liver Fibrosis ◽

Liver Function ◽

Pulmonary Blood Flow ◽

Fontan Procedure ◽

Bidirectional Cavopulmonary Shunt ◽

Pulmonary Arterial ◽

Cavopulmonary Shunt

Abstract Objective: We evaluatedadditional pulmonary blood flowat the time of bidirectional cavopulmonary shunt andits effectson the Fontan procedure andlong-term outcome of Fontan circulation and liver function.Methods: We included 22patients (16 boys, 6 girls) having undergonebidirectional cavopulmonary shunt with additional pulmonary blood flow between April 2002 and January 2016. Mean ageand body weight were 20 ±13 monthsand 7.5 ± 6.5 kg, respectively.We retrospectively evaluated the patients'clinical data,including cardiac catheterization data, liver function, and liver fibrosis markers.Results: All patients werealive with a New York Heart Association status of I at the long-term follow-up. Changes between pre-bidirectional cavopulmonary shunt and 101 months after the Fontan procedure included the following:the cardiothoracic ratio of chest X-ray decreased from 52.2 ± 3.9% to 41.8 ± 5.9% (p<0.001);systemic ventricle end-diastolic pressure decreased from 11.4±3.2 mmHg to 6.9±3.6mmHg(p<0.001);and the pulmonary artery index decreased from 485.1±272.3 to 269.5 ± 100.5(p=0.02). Type IV collagen, hyaluronic acid, and procollagen levels increased over the normal range 116 months after the Fontan procedure.Conclusions:The additional pulmonary blood flowat the time of bidirectional cavopulmonary shuntmaycontributeto pulmonary arterial growth at the Fontan procedure with low pulmonary arterial resistanceand without ventricle volumeoverload. The Fontan circulation was well-maintained at thelong-term follow-up, while liver fibrosis markerswere above their normal values.

Download Full-text

Incidence and predictors of new onset left ventricular diastolic dysfunction in asymptomatic patients with rheumatoid arthritis without overt cardiac disease

Monaldi Archives for Chest Disease ◽

10.4081/monaldi.2019.1053 ◽

2019 ◽

Vol 89 (3) ◽

Author(s):

Elena Costanza Dal Piaz ◽

Giovanni Cioffi ◽

Federica Ognibeni ◽

Andrea Dalbeni ◽

Alessandro Giollo ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Heart Failure ◽

Diastolic Dysfunction ◽

Cardiac Disease ◽

Multivariate Logistic Regression Analysis ◽

Left Ventricular ◽

Transmitral Flow ◽

Asymptomatic Patients ◽

New Onset

Rheumatoid arthritis (RA) is associated with higher risk of heart failure. Several studies report that left ventricular (LV) diastolic dysfunction (LVDD), a silent precursor of heart failure, is widely present in RA patients. Very little is known about the factors related to the development of LVDD in this disease. In this study we assessed the incidence and the predictors of new-onset LVDD in RA patients. Two-hundred-ninety-five adults with RA without overt cardiac disease were prospectively analyzed from March 2014 to March 2015 by Doppler echocardiography. Among the 295 subjects evaluated, 217 (73.6%) had normal LV diastolic function and represented the final study population. At 1-year follow-up, 53 of 217 patients (24%) developed LVDD, which was of degree I (mild dysfunction) in all of them. By multivariate logistic regression analysis, lower E/A ratio of transmitral flow (ratio between the peak velocity of early diastolic “E” wave and late diastolic “A” wave of transmitral flow) was independently associated with new-onset LVDD [OR 0.17 (CI 0.09-0.57)], together with older age and higher systolic blood pressure. In a clinical predictive model derived from multivariate analysis, the new-onset LVDD rate event ranged from 0% (patients without any factor) to 75% (patients in whom the three predictors coexisted). A significant portion of patients with RA without overt cardiac disease develop LVDD at 1-year follow-up. This condition can be predicted by a simple clinical model which could improve the clinical management and the prognostic stratification of patients with RA.

Download Full-text

Long-term results of additional pulmonary blood flow with bidirectional cavopulmonary shunt

10.21203/rs.3.rs-31559/v2 ◽

2020 ◽

Author(s):

Ryosuke Kowatari ◽

Yasuyuki Suzuki ◽

Kazuyuki Daitoku ◽

Ikuo Fukuda

Keyword(s):

Blood Flow ◽

Liver Fibrosis ◽

Pulmonary Blood Flow ◽

Fontan Procedure ◽

Bidirectional Cavopulmonary Shunt ◽

Long Term Follow Up ◽

Pulmonary Arterial ◽

Cavopulmonary Shunt

Abstract Objective: We evaluated additional pulmonary blood flow at the time of bidirectional cavopulmonary shunt and its effects on the Fontan procedure and long-term outcome of Fontan circulation and liver function.Methods: We included 22 patients (16 boys, 6 girls) having undergone bidirectional cavopulmonary shunt with additional pulmonary blood flow between April 2002 and January 2016. Mean age and body weight were 20 ± 13 months and 7.5 ± 6.5 kg, respectively. We retrospectively evaluated the patients' clinical data, including cardiac catheterization data, liver function, and liver fibrosis markers.Results: All patients were alive with a New York Heart Association status of I at the long-term follow-up. Changes between pre-bidirectional cavopulmonary shunt and 101 months after the Fontan procedure included the following: the cardiothoracic ratio of chest X-ray decreased from 52.2 ± 3.9% to 41.8 ± 5.9% (p < 0.001); systemic ventricle end-diastolic pressure decreased from 11.4 ± 3.2 mmHg to 6.9 ± 3.6 mmHg (p < 0.001); and the pulmonary artery index decreased from 485.1 ± 272.3 to 269.5 ± 100.5 (p = 0.02). Type IV collagen, hyaluronic acid, and procollagen levels increased over the normal range 116 months after the Fontan procedure.Conclusions: The additional pulmonary blood flow at the time of bidirectional cavopulmonary shunt may contribute to pulmonary arterial growth at the Fontan procedure with low pulmonary arterial resistance and without ventricle volume overload. The Fontan circulation was well-maintained at the long-term follow-up, while liver fibrosis markers were above their normal values.

Download Full-text