Long-Term Outcomes and Characteristics Associated With Mortality of Adult Patients Post Fontan Surgery: 27-Year Single-Center Experience

Abstract

Data on the characteristics and long-term outcomes of patients who underwent Fontan surgery and surviving into adulthood are limited. We aimed to describe our center's long-term experience with this unique patient population. Included were adult patients who had undergone Fontan surgery and were followed up at our Adult Congenital Heart Disease clinic between the years 1994 and 2021. We describe cardiac and noncardiac morbidities, medical treatment, laboratory data, echocardiographic characteristics, and all-cause mortality. The primary outcome was a composite of heart failure hospitalizations or death. A total of 107 patients who underwent Fontan surgery were followed up during the study period; 46.7% were male. The mean age at time of Fontan was 7.4 ± 6.2 years and the mean age at the last follow-up or at the time of an outcome event was 35.0 ± 8.0 years (range 21.1 to 62.8). At the last documented follow-up, 74.7% of the cohort were in New York Heart Association functional class I/II. The common morbidities included atrial arrythmias (37%) and stroke (17%). The primary outcome occurred in 17.7%. By the end of the study period, 9.3% of the patients in the cohort died. In a multivariate logistic regression analysis, controlling for gender, age, and Fontan type, worse functional class at the last follow-up (New York Heart Association III/IV vs I/II) was significantly associated with the risk of the primary outcome (odds ratio 34.57, 95% confidence interval 6.728 to 177.623, p <0.001). In conclusion, long-term outcomes of patients surviving into adulthood with a Fontan circulation is encouraging. Most of these patients achieve good functional cardiovascular status, despite the complex anatomy and a substantial burden of co-morbid conditions, specifically, atrial arrythmias and thrombotic events. Functional class was independently associated with heart failure hospitalizations and mortality. Data on the characteristics and long-term outcomes of patients who underwent Fontan surgery and surviving into adulthood are limited. We aimed to describe our center's long-term experience with this unique patient population. Included were adult patients who had undergone Fontan surgery and were followed up at our Adult Congenital Heart Disease clinic between the years 1994 and 2021. We describe cardiac and noncardiac morbidities, medical treatment, laboratory data, echocardiographic characteristics, and all-cause mortality. The primary outcome was a composite of heart failure hospitalizations or death. A total of 107 patients who underwent Fontan surgery were followed up during the study period; 46.7% were male. The mean age at time of Fontan was 7.4 ± 6.2 years and the mean age at the last follow-up or at the time of an outcome event was 35.0 ± 8.0 years (range 21.1 to 62.8). At the last documented follow-up, 74.7% of the cohort were in New York Heart Association functional class I/II. The common morbidities included atrial arrythmias (37%) and stroke (17%). The primary outcome occurred in 17.7%. By the end of the study period, 9.3% of the patients in the cohort died. In a multivariate logistic regression analysis, controlling for gender, age, and Fontan type, worse functional class at the last follow-up (New York Heart Association III/IV vs I/II) was significantly associated with the risk of the primary outcome (odds ratio 34.57, 95% confidence interval 6.728 to 177.623, p <0.001). In conclusion, long-term outcomes of patients surviving into adulthood with a Fontan circulation is encouraging. Most of these patients achieve good functional cardiovascular status, despite the complex anatomy and a substantial burden of co-morbid conditions, specifically, atrial arrythmias and thrombotic events. Functional class was independently associated with heart failure hospitalizations and mortality. The Fontan operation, initially described in 1971, has allowed the survival into adulthood of many patients born with single functioning ventricles.1Fontan F Baudet E Surgical repair of tricuspid atresia.Thorax. 1971; 26: 240-248Crossref PubMed Google Scholar Although many modifications have been devised over the years, they are all based on the concept of separation of systemic and pulmonary circulations, with the latter being “pumpless” and relying on hydrodynamic principles for pulmonary perfusion. Therefore, there exists an ever-growing population of Fontan patients, requiring optimal physiologic conditions to preserve cardiac function while being inherently susceptible to develop late complications and failure.2Deal BJ Jacobs ML Management of the failing Fontan circulation.Heart. 2012; 98: 1098-1104Crossref PubMed Scopus (112) Google Scholar With the demographics of this populations changing and more patients surviving into adulthood, individual patient-level data on the long-term outcomes are increasingly documented; nevertheless, contemporary data on real-world adult cohorts have rarely been reported.3d'Udekem Y Iyengar AJ Galati JC Forsdick V Weintraub RG Wheaton GR Bullock A Justo RN Grigg LE Sholler GF Hope S Radford DJ Gentles TL Celermajer DS Winlaw DS Redefining expectations of long-term survival after the Fontan procedure: twenty-five years of follow-up from the entire population of Australia and New Zealand.Circulation. 2014; 130: S32-S38Crossref PubMed Scopus (434) Google Scholar, 4Pundi KN Johnson JN Dearani JA Pundi KN Li Z Hinck CA Dahl SH Cannon BC O'Leary PW Driscoll DJ Cetta F 40-year follow-up after the Fontan operation: long-term outcomes of 1,052 patients.J Am Coll Cardiol. 2015; 66: 1700-1710Crossref PubMed Scopus (424) Google Scholar, 5Khairy P Fernandes SM Mayer Jr, JE Triedman JK Walsh EP Lock JE Landzberg MJ Long-term survival, modes of death, and predictors of mortality in patients with Fontan surgery.Circulation. 2008; 117: 85-92Crossref PubMed Scopus (784) Google Scholar In this study, we set out to describe the long-term outcomes of adults after Fontan surgery followed up at our referral center Adult Congenital Heart Disease (ACHD) clinic. Included were consecutive patients who underwent Fontan surgery and were followed up at the ACHD Clinic at Rabin Medical Center between January 1994 and December 2021. The overwhelming majority of patients underwent the operation before the first presentation at our clinic. The data were collected retrospectively. Detailed demographic and clinical data were extracted from patient files and electronic records; this included data from diagnostic tests, functional status as assessed by clinic physicians during follow-up visits, echocardiographic data as performed by dedicated cardiac sonographers with extensive experience in the ACHD population, and surgical and hemodynamic study data when available. Liver pathology on ultrasound was defined as any abnormality stated, including liver nodules, fibrosis, and cirrhotic findings. A major bleeding event was defined as any intracranial, gastrointestinal, gynecologic hemorrhage, hemoptysis, or other bleeding event necessitating blood transfusion or hospital admission. Pulmonary veno-venous collaterals were diagnosed on computer tomography or with angiography in the catheterization laboratory. Data on mortality were derived from the notification of death form legally required by the Israeli Ministry of Interior Affairs. The primary outcome was a composite of death or heart failure hospitalization (HFH). The secondary outcomes assessed were cardiac and noncardiac morbidity, hospitalizations for heart failure, and all-cause mortality. This study received ethics board approval from the Rabin Medical Center institutional ethics committee. The baseline characteristics of the patients are presented for the whole cohort as means (SD)/medians (interquartile range [IQR]) for continuous variables, and counts (%) for categorical variables, as appropriate. Continuous variables were compared between groups using the Student's t test; categorical variables were compared using the chi-square test, as appropriate. All tests were 2-tailed, and a p <0.05 was considered significant. For the risk model, all nonmissing variables (cutoff 90%) found to be associated with HFH or death in univariate analysis at a threshold of p <0.25 were entered into a multivariable logistic regression model. The multicollinearity between included covariates was assessed using variance inflation factor. Model quality was assessed using the Akaike and Bayesian information criteria; model discrimination was assessed using the area under the receiver-operator curve or the c-statistic. The group differences in all-cause mortality were assessed using the Kaplan–Meier method, compared between groups using the log-rank test, and graphically plotted using Kaplan–Meier curves. Our cohort included 107 patients with Fontan physiology. The baseline characteristics are listed in Table 1. Biomarkers, echocardiographic findings, and medications at the time of the last follow-up visit are listed in Table 2. The primary cardiac pathology is displayed in Figure 1. The mean age at time of Fontan was 7.4 ± 6.2 years. The histograms of age at Fontan surgery and Fontan type are shown in Figure 2, Figure 3, respectively. The mean age at the first ACHD visit was 28 ± 7 years. The median duration of follow-up at the clinic after the Fontan operation was 28 years (IQR 22 to 31 years). The mean age at last follow-up or death was 35.0 ± 8.0 years (range 21.1 to 62.8 years), as shown in Figure 4. A total of 79 patients had a systemic morphologic left ventricle, 25 patients had a systemic morphologic right ventricle, and 3 had a biventricular Fontan.Table 1Baseline characteristics of the cohortVariableCategoriesn (% of total or within category) / mean (SD) or median (IQR)N=107Male50 (46.7%)Age at last Follow-Up or death (years)35 (8)Age at surgery (years)7.37 (6.26)Time from surgery to last FU or death (years)28 (22-31)Fontan typeLateral tunnel54 (51.9%)Extra cardiac39 (37.5%)Bjork4 (3.8%)Atriopulmonary7 (6.7%)O2 saturation, baseline (%)93 (90-95)Hypertension3 (3%)Diabetes Mellitus1 (1%)Dyslipidemia7 (7%)Family history of congenital heart disease2 (2%)Data are presented as percentage, mean (SD) or median (IQR) as appropriate. Open table in a new tab Table 2Laboratory, echocardiographic results and medications at last follow upHemoglobin (g/dL)15.1 (13.85-16.7)Creatinine (mg/dL)0.78 (0.68-0.90)Alanine transaminase25 (15-33)Albumin (g/dL)4.4 (3.95-4.6)AV valve regurgitationNone32 (34%)Mild48 (51%)Mild-Moderate13 (14%)Moderate1 (1%)Mechanical AV valve2 (2%)Systemic Ventricle ejection fractionPreserved EF ( ≥ 50)77 (79%)Mildly reduced EF (≥ 40)18 (18%)Reduced EF (<40)3 (3%)Beta blocker19 (19%)ACE/ARB65 (66%)Aspirin29 (29%)Calcium Channel Blocker3 (3%)Digoxin16 (16%)Anticoagulation66 (62%)Indication for anticoagulationAtrial arrhythmia20 (30%)Primary prevention of thrombotic event31 (50%)Secondary prevention of thrombotic event15 (23%)AV = atrioventricular; ACE/ARB= angiotensin-converting enzyme inhibitors/angiotensin receptor blockers. Open table in a new tab Figure 2Age at time of Fontan surgery.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Figure 3Fontan type in our cohort.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Figure 4Mean age of Fontan surgery and mean age at last FU/death. FU = follow up.View Large Image Figure ViewerDownload Hi-res image Download (PPT) Data are presented as percentage, mean (SD) or median (IQR) as appropriate. AV = atrioventricular; ACE/ARB= angiotensin-converting enzyme inhibitors/angiotensin receptor blockers. A total of 74.7% of the cohort were in New York Heart Association (NYHA) functional class I/II at the last follow-up. Few patients had reduced ejection fraction on echocardiography (3%) and fewer still had moderate or greater atrioventricular (AV) valve regurgitation (1%). During the study period, 15% of the cohort had an admission for decompensated heart failure symptoms. Table 3 lists the co-morbidities of the cohort: 10 patients underwent percutaneous interventional procedures, including 3 pulmonary venous-venous collateral embolization procedures, 3 Fontan procedures, left pulmonary and with an and percutaneous valve in patients with a and during adult follow up of the pathology on hemodynamic bleeding bleeding failure = cardiac = = = Open table in a new tab = cardiac = = = A total of patients underwent cardiac surgical during follow-up, including patients with AV valve patients with Fontan with and 3 with patient who underwent surgery for of the and patient who underwent surgery for valve were common in the with an atrial and a of patients underwent an A total of patients had a was in this with with atrial as for treatment, as secondary prevention after a thrombotic and as a primary The of thrombotic and bleeding are listed in Table was a substantial in patients (17%). The cohort had cardiovascular risk over a of the cohort had a on liver ultrasound age of this was ± 7 years), and there was a single of Pulmonary veno-venous collaterals were in The majority of the cohort with at the last follow-up. was as a of Fontan in 3 patients A total of of the in the cohort were the follow-up period; the of these patients was (IQR to with an of (IQR to The was in of all A patient clinical heart failure during were of death in the The composite outcome occurred in patients, of death occurred in 10 patients and HFH during adult follow-up in 7 patients who were for HFH died. The univariate analysis of with the composite outcome of HFH or death is listed in Table 4. Fontan type was significantly associated with the composite outcome = Fontan was the Fontan type in patients who the composite was the in who and were in event the risk in these was in the composite outcome into the of the systemic or the baseline congenital the composite outcome were 3 more to be in functional class III/IV I/II to have vs p = to have = to have liver pathology on to have a AV valve and to have a = ejection fraction was = as was = an = or atrial = analysis for composite outcome of HFH or composite outcome outcome at last up or death at surgery from surgery to last or death (years)28 typeLateral Heart of the at last saturation, baseline (%)93 pathology on (mg/dL)0.78 valve AV ejection EF ( ≥ reduced EF (≥ EF bleeding are presented as percentage, mean (SD) or median (IQR) as = angiotensin-converting enzyme inhibitors/angiotensin receptor = atrioventricular; = cardiac = EF = ejection HFH = heart failure = = left = New York Heart Association functional = Open table in a new tab Data are presented as percentage, mean (SD) or median (IQR) as appropriate. = angiotensin-converting enzyme inhibitors/angiotensin receptor = atrioventricular; = cardiac = EF = ejection HFH = heart failure = = left = New York Heart Association functional = The results from a multivariate logistic regression model of the between and outcome are listed in Table in III/IV had an ratio for the composite end of confidence interval 6.728 to 177.623, p compared with in I/II at the last follow-up shown in Figure age at the last follow-up, Fontan type, and cardiac pathology were for and significantly associated with the composite outcome on the multivariate logistic analysis for risk of composite of heart failure hospitalization or ratio of at last Follow-Up at last Follow-Up or Fontan = ejection HFH = heart failure = New York Heart Association functional Open table in a new tab EF = ejection HFH = heart failure = New York Heart Association functional During the study period, 10 patients died. The of death were decompensated heart failure failure in and cardiac in The Kaplan–Meier mortality of the cohort from age years is shown in Figure The Kaplan–Meier survival for the cohort was to at 10 years of follow-up, to at years of follow-up, and to at years of follow-up. Our patients surviving into the of adulthood with a Fontan circulation have a good of these patients good functional class and cardiac patients have co-morbid conditions to be associated with the Fontan specifically, atrial arrythmias and thrombotic events. the of the anatomy and the mortality in adults patients surviving to the and is The Fontan operation to a circulation in there is systemic pulmonary reduced in a cardiac P S of the Fontan operation: a of on outcomes after Heart PubMed Scopus Google Scholar This circulation is and more susceptible to in blood and function a to cardiac and Our results are and with other survival for this Y Iyengar AJ Galati JC Forsdick V Weintraub RG Wheaton GR Bullock A Justo RN Grigg LE Sholler GF Hope S Radford DJ Gentles TL Celermajer DS Winlaw DS Redefining expectations of long-term survival after the Fontan procedure: twenty-five years of follow-up from the entire population of Australia and New Zealand.Circulation. 2014; 130: S32-S38Crossref PubMed Scopus (434) Google Scholar, 4Pundi KN Johnson JN Dearani JA Pundi KN Li Z Hinck CA Dahl SH Cannon BC O'Leary PW Driscoll DJ Cetta F 40-year follow-up after the Fontan operation: long-term outcomes of 1,052 patients.J Am Coll Cardiol. 2015; 66: 1700-1710Crossref PubMed Scopus (424) Google Scholar, 5Khairy P Fernandes SM Mayer Jr, JE Triedman JK Walsh EP Lock JE Landzberg MJ Long-term survival, modes of death, and predictors of mortality in patients with Fontan surgery.Circulation. 2008; 117: 85-92Crossref PubMed Scopus (784) Google Scholar described as a many of these patients are surviving into data on the long-term and mortality of these patients is limited. The outcomes the Australia and New Fontan in a survival at 25 years after the Fontan surgery was Pundi KN Johnson JN Dearani JA Pundi KN Li Z Hinck CA Dahl SH Cannon BC O'Leary PW Driscoll DJ Cetta F 40-year follow-up after the Fontan operation: long-term outcomes of 1,052 patients.J Am Coll Cardiol. 2015; 66: 1700-1710Crossref PubMed Scopus (424) Google Scholar a survival at years of follow-up in Y Iyengar AJ Galati JC Forsdick V Weintraub RG Wheaton GR Bullock A Justo RN Grigg LE Sholler GF Hope S Radford DJ Gentles TL Celermajer DS Winlaw DS Redefining expectations of long-term survival after the Fontan procedure: twenty-five years of follow-up from the entire population of Australia and New Zealand.Circulation. 2014; 130: S32-S38Crossref PubMed Scopus (434) Google KN Johnson JN Dearani JA Pundi KN Li Z Hinck CA Dahl SH Cannon BC O'Leary PW Driscoll DJ Cetta F 40-year follow-up after the Fontan operation: long-term outcomes of 1,052 patients.J Am Coll Cardiol. 2015; 66: 1700-1710Crossref PubMed Scopus (424) Google Scholar Our a Kaplan–Meier survival of after years of follow-up. We found were associated with the outcome of death or Most of these have been Celermajer DS BJ Y Heart Association on Disease in the and on and and of the and adult with Fontan a from the Heart PubMed Scopus Google Scholar our with a AV valve are more to have the composite outcome to the of our been The AV valve an in the Fontan and the regurgitation of this valve is a for mortality in patients with Fontan Celermajer DS BJ Y Heart Association on Disease in the and on and and of the and adult with Fontan a from the Heart PubMed Scopus Google Scholar Pundi KN Johnson JN Dearani JA Pundi KN Li Z Hinck CA Dahl SH Cannon BC O'Leary PW Driscoll DJ Cetta F 40-year follow-up after the Fontan operation: long-term outcomes of 1,052 patients.J Am Coll Cardiol. 2015; 66: 1700-1710Crossref PubMed Scopus (424) Google Scholar AV valve repair or at the time of Fontan was significantly associated with a risk of or death. 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