Thromboembolic Complications in Adult Patients Following Fontan Procedure-A Multicenter Study.

BACKGROUND: Morbidity and mortality following Fontan (FO) surgery are primarily thromboembolic in nature. However, follow-up data regarding thromboembolic complications (TECs) in adult patients after FO procedure are inconsistent. In this multicenter study, we investigated the incidence of TECs in FO patients. METHODS: We studied 91 patients who underwent FO procedure. Clinical data, laboratory, and imaging investigations were collected prospectively during the scheduled medical appointments in 3 Adult Congenital Heart Disease Departments in Poland. TECs were recorded during a median follow-up of 31 months. RESULTS: Four patients (4.4%) were lost to follow-up. The mean age of patients was 25.3 (±6.0) years at enrollment, and the mean time between FO operation and investigation was 22.1 (±5.1) years. A total of 21 out of 91 patients (23.1%) had a history of 24 TECs since an FO procedure, mainly pulmonary embolism (PE; n = 12, 13.2%), including 4 (33.3%) silent PE. The mean time since FO operation to the first TEC was 17.8 (±5.1) years. During follow-up, we documented 9 TECs in 7 (8.0%) patients, mainly PE (n = 5, 5.5%). Most patients with TEC had a left type of systemic ventricle (57.1%). Three patients (42.9%) were treated with aspirin, 3 (3.4%) with Vitamin K antagonists or novel oral anticoagulants, and 1 patient had no antithrombotic treatment at the time of TEC occurrence. Supraventricular tachyarrhythmias were present in 3 patients (42.9%). CONCLUSIONS: This prospective study shows that TECs are common in FO patients, and a significant number of these events occur during adolescence and young adulthood. We also indicated how much TECs are underestimated in the growing adult FO population. The complexity of the problem requires more studies, especially to standardize the prevention of TECs in the whole FO population.

Properties of Plasma Clots in Adult Patients Following Fontan Procedure: Relation to Clot Permeability and Lysis Time-Multicenter Study.

OBJECTIVES: thromboembolic complications are a major cause of morbidity and mortality following Fontan (FO) surgery. It is also well established that altered FO circulation results in systemic complications, including liver and endothelium damage. We sought to evaluate whether dysfunctions of these sources of hemostatic factors may result in changes of fibrin clot properties. METHODS: a permeation coefficient (Ks) and clot lysis time (CLT) were assessed in 66 FO patients, aged 23.0 years [IQR 19.3-27.0], and 59 controls, aged 24.0 years [IQR 19.0-29.0]. Ks was determined using a pressure-driven system. CLT value was measured according to assay described by Pieters et al. Endothelium and liver-derived hemostatic factors along with liver function parameters were evaluated. The median time between FO operation and investigation was 20.5 years [IQR 16.3-22.0]. RESULTS: FO patients had lower Ks (p = 0.005) and prolonged CLT (p < 0.001) compared to that of controls. Ks correlated with CLT (r = -0.28), FVIII (r = -0.30), FIX (r = -0.38), fibrinogen (r = -0.41), ALT (r = -0.25), AST (r = -0.26), GGTP (r = -0.27) and vWF antigen (r = -0.30), (all p < 0.05). CLT correlated with the time between FO operation and investigation (r = 0.29) and FIX (r = 0.25), (all p < 0.05). After adjustment for potential cofounders, TAFI antigen and GGTP were independent predictors of reduced Ks (OR 1.041 per 1% increase, 95% CI 1.009-1.081, p = 0.011 and OR 1.025 per 1 U/L increase, 95% CI 1.005-1.053, p = 0.033, respectively). Protein C and LDL cholesterol predicted prolonged CLT (OR 1.078 per 1% increase, 95% CI 1.027-1.153, p = 0.001 and OR 6.360 per 1 µmol/L increase, 95% CI 1.492-39.894, p = 0.011, respectively). Whereas elevated tPA was associated with lower risk of prolonged CLT (OR 0.550 per 1 ng/mL, 95% CI 0.314-0.854, p = 0.004). GGTP correlated positively with time between FO surgery and investigation (r = 0.25, p = 0.045) and patients with abnormal elevated GGTP activity (n = 28, 42.4%) had decreased Ks, compared to that of the others (5.9 × 10-9 cm2 vs. 6.8 × 10-9 cm2, p = 0.042). CONCLUSION: our study shows that cellular liver damage and endothelial injury were associated with prothrombotic clot phenotype reflected by Ks and CLT.

Noninvasive assessment of liver status in adult patients after the Fontan procedure.

INTRODUCTION A hemodynamic derangement in Fontan circulation causes liver pathology known as Fontan­­associated liver disease. Although liver biopsy is a standard for diagnosis of liver fibrosis, noninvasive methods are being developed, including shear wave elastography (SWE). OBJECTIVES We aimed to evaluate the degree of liver stiffness (LS) using SWE in patients with Fontan circulation in a long­­term follow­­up and to investigate a relationship between patient characteristics and LS. PATIENTS AND METHODS The study included 59 patients after the Fontan procedure. Clinical examinations and laboratory tests were performed. According to the stage of LS, patients were divided into 2 subgroups: group 1 (METAVIR stages F1 and F2) and group 2 (METAVIR stages F3 and F4). The ratio of aspartate transaminase to alanine transaminase, aspartate transaminase­­to­­platelet ratio index (APRI), fibrosis­­4 (FIB­­4) score, and Forns index were assessed. RESULTS The median LS was 9.1 kPa (interquartile range, 3.9-18.5 kPa). Five patients (9%) demonstrated LS in stage F1; 14 (26%), F2; 28 (52%), F3; and 7 (13%), F4. Group 2 had significantly higher aspartate transaminase and γ­­glutamyltranspeptidase levels, APRI, FIB­­4, and Forns index, and lower platelet count than group 1. A canonical correlation analysis indicated that LS and thrombocytopenia were related to time from the Fontan procedure, age at procedure, and single ventricular ejection fraction. CONCLUSIONS We showed that adult patients after the Fontan procedure develop liver dysfunction. Time from surgery, age at procedure, and single ventricular ejection fraction are related to the degree of LS assessed by SWE. Finally, SWE, APRI, Forns index, and FIB­4 score may help assess the degree of liver fibrosis.

Assessment of Left Atrial Function in Patients with Paroxysmal, Persistent, and Permanent Atrial Fibrillation using Two-Dimensional Strain.

BACKGROUND AND PURPOSE: Atrial fibrillation (AF) has a progressive nature, leading to structural, functional, and electrical changes in the left atrium (LA). Enhanced response to treatment in patients with AF can be achieved through improved knowledge of atrial structure and a better understanding of its function. The aim of this study was to assess LA strain and its determinants in patients with paroxysmal (PAF), persistent (PsAF), and permanent AF (PmAF). METHODS: Fifty-eight patients with registered non-valvular AF were divided into 3 groups depending on the type of AF. The participants underwent transthoracic echocardiography to assess the anatomy and function of heart chambers. Left atrial longitudinal strain (LALS) was measured in four-chamber projections using two-dimensional speckle tracking echocardiography. RESULTS: Patients with PAF had higher LALS (15.7±12.0) when compared to those with PsAF (4.3±7.9) and PmAF (5.8±7.8, all P=0.003). Multiple linear regression showed that the independent predictors of LALS were diastolic blood pressure (ß=0.95, R2=0.88) in the PAF group; left atrial area (ß=-0.56) and creatinine (ß=-0.63, R2=0.58) in the PsAF group; AF duration (ß=0.89) in the PmAF group (R2=0.72). CONCLUSION: LA strain has different determinants depending on AF type. LA size, renal function, and AF duration determine LALS in long-lasting AF. LA strain is a simple and accurate technique to estimate LA dysfunction in patients with long-lasting AF.

Long-term follow-up in adults after tetralogy of Fallot repair.

BACKGROUND: Tetralogy of Fallot (ToF) is the most common cyanotic congenital heart disease and the population of ToF repair survivors is growing rapidly. Adults with repaired ToF develop late complications. The aim of this study was to describe and analyze long-term follow-up of patients with repaired ToF. METHODS: This is a retrospective cohort study. Consecutive 83 patients with repaired ToF who did not undergo pulmonary valve replacement were included. Mean age of all patients was 30.5 ± 10.7. There were 49 (59%) male. Patients were divided into two groups according to the time since the repair (< 25 years and ≥ 25 years). The electrocardiographic (ECG), cardiopulmonary exercise testing (CPET), echocardiographic and cardiac magnetic resonance (CMR) data were reviewed retrospectively. RESULTS: In CPET values were not significantly different in the two groups. In CMR volumes of left and right ventricles were not significantly different in the two groups. There were no differences between the groups in ventricular ejection fraction, mass of ventricles, or pulmonary regurgitation fraction. Among all the patients, ejection fraction and left and right ventricle mass, indexed pulmonary regurgitation volume measured by CMR did not correlate with the time since repair. In ECG among all the patients, ejection fraction of the RV, measured in CMR, negatively correlated with QRS duration (r = - 0.43; p < 0.001). There was a positive correlation between QRS duration and end diastolic volume of the RV (r = 0.30; p < 0.02), indexed end diastolic volume of the RV (r = 0.29; p = 0.04), RV mass (r = 0.36; p < 0.001) and left ventricle mass (r = 0.26; p = 0.04). CONCLUSION: Long-term survival and clinical condition after surgical correction of ToF in infancy is generally good and the late functional status in ToF - operated patients could be excellent up to 25 years after the repair. QRS duration could be an utility and easy factor to assessment of right ventricular function. TRIAL REGISTRATION: The study protocol was approved by the local Ethics Committee. Each participant provided informed consent to participate in the study (license number 122.6120.88.2016 from 28.04.2016).

[Cardiovascular risk factors in patients after coarctation of aorta repair]. / Czynniki ryzyka chorób sercowo-naczyniowych u chorych po leczeniu interwencyjnym koarktacji aorty.

The coarctation of the aorta (CoA) is a congenital condition of the thoracic aorta. AIM: The aim of the study was assessment of atherosclerosis risk factors in adult patients after surgical treatment of aortic coarctation. MATERIALS AND METHODS: 58 patients (36 male, 22 female) at median age of 27.46 ±10.57 were compared with 30 healthy, age and sex matched volunteers. The arterial blood pressure, lipid profile, fasting glucose, inflammation markers and the lifestyle factors were analyzed. RESULTS: CoA patients have higher systolic blood pressure 136.55±16.27 vs 123.47±10.34 mmHg, p<0.001, fasting glucose 4.95±0.5 vs 4.65±0.46 mmol/l p=0.002, hsCRP 1.03±0.12 vs 0.89±0.14 mg/l p=0.025 and fibrinogen 2.55±0.34 vs 1.98±0.28 g/l p<0.001. Hyperlipidemia is more common 44.8% vs 23.3% p=0.048, treated with statin. When comparing hypertensive patients (N=28) with normotensive ones (N=30), the patients with arterial hypertension are older 33.5±12.23 vs 25.73±7.12 p=0.004, have higher body weight 78.03±14.58 vs 68.7±14.29 p=0.017, in this group more common are: hypoplastic aortic arch 28.6% vs 6.7% p=0.027, recoarctation 39.3% vs 13.3% p=0.024, cardiovascular disease 14.3% vs 0% p=0.032 and family history 21.4% vs 3.3% p=0.034. CONCLUSIONS: The coarctation of aorta is related to higher cardiovascular risk due to arterial hypertension, hyperlipidemia, higher glucose and inflammation markers levels when comparing with healthy population.

Long-Term Effects of Percutaneous Fenestration Following the Fontan Procedure in Adult Patients with Congenital Univentricular Heart.

BACKGROUND The Fontan procedure, performed for univentricular heart, may also include the technique of percutaneous fenestration to create a small atrial septal defect (ASD) and a right-to-left shunt. The aim of this study was to evaluate the long-term effects of fenestration in adult patients who had a Fontan procedure for univentricular heart. MATERIAL AND METHODS Fontan surgery was performed in 39 patients, including 19 (49%) patients with fenestration (Group I), and 20 (51%) patients without the fenestration procedure (Group II). Laboratory tests in both groups included echocardiography, plethysmography, cardiopulmonary exercise testing, and 24-hour Holter monitoring. RESULTS Compared with patients in Group I, patients in Group II had a significantly increased level of N-terminal pro-brain natriuretic peptide (NT-proBNP) (p=0.04), alkaline phosphatase (ALP) (p=0.01) and a significant increase in frequency of atrial fibrillation (p=0.04). Patients in Group I had a significantly increased systemic ventricular ejection fraction (SVEF) (p=0.05) and increased heart rate (HR) (p=0.006), heart rate reserve (HRR) (p=0.02), ventilatory equivalent (VE) (p=0.01), and VO2 peak (p=0.05) on cardiopulmonary exercise testing (CPET). Renal, hematologic, and ventilatory parameters, and incidence of thromboembolism showed no significant differences between the groups. CONCLUSIONS Long-term follow-up of patients who underwent Fontan procedures with percutaneous fenestration had improved single ventricular function, lower NT-proBNP levels, improved exercise capacity, and reduced ALP levels. These findings indicate that percutaneous fenestration closure should be considered for adult patients who have undergone Fontan procedure for univentricular heart.

What determines the quality of life of adult patients after Fontan procedure?

BACKGROUND: Despite the low early mortality of Fontan procedures, Fontan patients are prone to vari-ous cardiac and extra-cardiac complications in the long term. This may influence patient perception of their health and outcome. The aim of the study was to assess the relationship of multi-organ compli-cations and physical efficiency with self-reported health-related quality of life (QOL) in adult Fontan patients. METHODS: Quality of life was assessed with the Short Form-36 questionnaire. Laboratory tests were done together with echocardiography, plethysmography, and cardiopulmonary exercise test. RESULTS: The QOL was poorer in patients than in control subjects. The physical characteristics of patients correlated with dynamic ventilatory parameters, heart rate at the peak of exercise, alanine aminotransferase and albumin level. CONCLUSIONS: Liver impairment and chronotropic incompetence during exercise are associated with poor QOL in patients after Fontan procedure. In these patient, hepatic, pulmonary and cardiac functions should be carefully monitored. (Cardiol J 2018; 25, 1: 72-80).

[Evaluation of the clinical suitability of automated left ventricle's fraction and volume measurements in 3-dimensional echocardiography compared to values obtained in magnetic resonance imaging (pilot study)]. / Ocena przydatnosci klinicznej automatycznego pomiaru frakcji i objetosci lewej komory w echokardiografii przezklatkowej 3D w porównaniu do wartosci uzyskanych w rezonansie magnetycznym (badanie pilotazowe).

Recently a lot of authors have been trying to determine the usefulness of 3-dimensional echocardiography (TTE 3D) in evaluation of ejection fraction and left ventricular volume, but few attempt to compare it to the current gold standard of cardiac magnetic resonance (CMR). 3D imaging technics allows to avoid errors caused by geometry of the heart chambers and foreshortened views. American Echocardiographic Guidelines recommend the use of 3-dimensional echocardiography in daily clinical practice. AIM: The aim of the study was to establish clinical usefulness of automated 3D TTE software to calculate left ventricle ejection fraction (LVEF), left ventricle end diastolic volume (LVEDV) and left ventricle end systolic volume (LVESV), and to compare those measurements calculated in CMR and in 3D TTE. MATERIALS AND METHODS: The aim of the study was to establish clinical usefulness of automated 3D TTE software to calculate left ventricle ejection fraction (LVEF), left ventricle end diastolic volume (LVEDV) and left ventricle end systolic volume (LVESV), and to compare those measurements calculated in CMR and in 3D TTE. RESULTS: The mean LVEF in 3D TTE was 65% +/- 12%; LVEDV 123 ml +/- 67 ml, LVESV 42 ml +/- 29 ml. The CMR LVEF in the study group was 61% +/- 9%, LVEDV 134 ml +/- 51ml, LVESV 54 ml +/- 33 ml. Wilcoxon rank test showed no difference between medians of the measurements, the correlation coefficient between LVEF in 3D TTE and CMR was R = 0.84 (p = 0.036). LVEF calculated in 3D TTE shows good correlation with LVEF computed in CMR. However good visualization of the endocardium, especially in the apex, is essential. The volume of left ventricle is underestimated in 3D TTE. In previous studies underestimation of LVEDV and LVESV was explained by exclusion of endocardial trabeculae from the left ventricle cavity in automated measurement. CONCLUSIONS: The automated 3D TTE software allows simple, fast and precise evaluation of parameters of the left ventricle - especially LVEF. Automated 3D TTE software gives hope for the inclusion of 3D TTE in routine clinical practice due to its repeatability and easy use of the Heart Model software.

[Multiorgan malfunction after Fontan operation in adult patients]. / Powiklania narzadowe u doroslych chorych po operacji Fontana.

Although 85% of patients with univentricular heart after Fontan procedure survive twenty years after operation, the procedure alone seems to be an inadequate treatment as a permanent clinical solution. Patients with a "Fontan physiology" additionally have to face a various extra-cardiac complications, including thyroid, liver and kidney dysfunction, which are not only potentially life-threatening, but also can potentiate the circulatory insufficiency. AIM: The aim of the study was to assess a multiorgan dysfunction in adult patients after Fontan operation in long term follow-up and compare to healthy controls. MATERIALS AND METHODS: 54 patients after Fontan procedure (age=25.1±7 years, time after operation =19.8±6.3 years, age at the time of the procedure =5.3±4.3 years) and 30 controls (26.2±5.8 years) were included to the study. Clinical and laboratory examinations were performed including: hematologic, hepatic, renal and thyroid function tests. The following laboratory tests were performed: red blood cell counts (RBC), hematocrit (Ht), hemoglobin (Hb), platelets count, red blood cell distribution width (RDW), iron level; Btype natriuretic peptide (NT-proBNP), proteinogram blood test, alanine aminotransferase (ALT), aspartate aminotransferase (AST), gammaglutamyl transpeptidase (GGTP), alkaline phosphatase (ALP), total bilirubin, alpha fetoprotein (AFP) level. Furthermore creatinine level; cystatin C, urine albumin to creatynine ratio (ACR) and urinalysis were assessed. To assess a thyroid function free triiodothyronine (fT3), free thyroxine (fT4) and thyroid stimulating hormone (TSH) were measured. Furthermore an abdomen ultrasonography was performed. RESULTS: In terms of the hematological disorders Fontan patients had a statistically significant higher level of RBC (5.6±0,8 vs 4.8±0.4 109/µl; p<0,001), Hb (16.5±2.8 vs 14.2±1.2 g/dl; p<0,001), HCT (48.7±8.1 vs 42.1±3 %; p<0,001), RDW (14±2.6 vs 12.8±0.5 %; p=0.001), as compared to control group, while PLT level was statistically lower in Fontan group (156.2±61.4 vs 224.2±48 103/µl; p<0,0001). Hepatic parameters in Fontan patients were statistically significant higher, as depicted by the level of: ALT (28.5±10.5 vs 21.5±6 U/l, p<0,001), GGTP (85.6±48.8 vs 19.3±9 U/ l, p<0,001), total bilirubin (26.6±24.8 vs 8.9±4.7 µmol/l; p<0,001), ALP (82.4±31.5 vs 51.2±16 U/l; p<0,001) and INR (1.21±0.3 vs 0.98±0.2; p<0,001). Other parameters such as: AFP, total protein and albumin level did not statistically significantly differ. Additionally five patients (9%) according to clinical symptoms and serum albumin level were diagnosed protein-losing enteropathy (PLE). There was no difference in serum creatinine level between Fontan patients and control group (79.6±23.6 vs 75.9±18.9 µmol/l; p=0.8) as well as in uric acid level (342.7±102 vs 303±105 µmol/l; p=0.2). Cystatin C level was significantly higher in Fontan group in comparison to controls (1.1±0.6 vs 0.8±0.1 ng/ml; p=0,05). Furthermore four Fontan patients (7%) had abnormal microalbumin/creatynine ratio. Urine testing preformed in 30 Fontan patients pointed to 7 cases (23%) where hematuria was observed, while proteinuria was detected in 4 cases (13%) and urobilinogen in 2 (7%). Dysfunction of the thyroid gland was found in 30% of patients after Fontan operation (7% in the control group, p=0,034). Among disorders of the thyroid gland: 13% of patients were diagnosed with hyperthyroidism, 54% diagnosed with subclinical hypothyroidism, and the remaining 33% with hypothyroidism. CONCLUSIONS: Our study show that adult patients after Fontan procedure in long-term follow are exposed to multiorgan complications including hematological, liver, kidney and thyroid dysfunction.

Secondary prevention in patients after hospitalisation due to coronary artery disease: what has changed since 2006?

BACKGROUND: The evidence concerning the quality of secondary prevention of coronary artery disease (CAD) in Poland in recent years is scarce. AIM: To compare the implementation of secondary prevention guidelines into everyday clinical practice between 2006-2007 and 2011-2012 in patients after hospitalisation due to CAD. METHODS: Five hospitals with departments of cardiology serving a city and its surrounding districts in the southern part of Poland participated in the study. Consecutive patients aged ≤ 80 years, hospitalised from April 1, 2005 to July 31, 2006 (first survey) and from April 1, 2010 to June 30, 2011 (second survey) due to acute coronary syndrome or for a myocardial revascularisation procedure were recruited and interviewed 6-18 months after hospitalisation. RESULTS: Medical records of 640 patients were reviewed and included in the first survey and 466 in the second survey. The proportion of medical records with available information on smoking did not differ between the surveys, whereas the proportion of medical records with available information on blood pressure and total cholesterol was lower in patients hospitalised in 2010-2011. The prescription rate of ß-blockers at discharge decreased from 90% to 84% (p < 0.05), whereas the prescription rates at discharge of other drug classes did not change significantly. The proportion of patients with high blood pressure (≥ 140/90 mm Hg) one year after hospitalisation decreased in 2011-2012 compared to 2006-2007 (from 48% to 35%, p < 0.05), whereas the proportion of subjects with high LDL cholesterol, high fasting glucose, and obesity did not change significantly. We did not note a significant difference in the smoking rate. The proportions of patients taking an antiplatelet agent (90% vs. 91%), a ß-blocker (87% vs. 79%), an ACE inhibitor or a sartan (79% vs. 76%), a calcium antagonist (22% vs. 25%), a diuretic (35%vs. 45%), and a lipid-lowering drug (86% vs. 87%) one year after discharge did not change significantly (all p > 0.05). CONCLUSIONS: We noted a modest improvement in the implementation of CAD secondary prevention guidelines in everyday clinical practice: blood pressure was better controlled, although the control of all other main risk factors did not change significantly. Our data provides evidence that there is a considerable potential for further reduction of cardiovascular risk in CAD patients.