Recurrent alcohol-associated hepatitis is common and is associated with increased mortality.

BACKGROUND AND AIMS: Alcohol relapse after surviving an episode of alcohol-associated hepatitis (AH) is common. However, the clinical features, risk factors, and prognostic implications of recurrent alcohol-associated hepatitis (RAH) are not well described. APPROACH AND RESULTS: A registry-based study was done of patients admitted to 28 Spanish hospitals for an episode of AH between 2014 and 2021. Baseline demographics and laboratory variables were collected. Risk factors for RAH were investigated using Cox regression analysis. We analyzed the severity of the index episodes of AH and compared it to that of RAH. Long-term survival was assessed by Kaplan-Meier curves and log-rank tests. A total of 1118 patients were included in the analysis, 125 (11%) of whom developed RAH during follow-up (median: 17 [7-36] months). The incidence of RAH in patients resuming alcohol use was 22%. The median time to recurrence was 14 (8-29) months. Patients with RAH had more psychiatric comorbidities. Risk factors for developing RAH included age <50 years, alcohol use >10 U/d, and history of liver decompensation. RAH was clinically more severe compared to the first AH (higher MELD, more frequent ACLF, and HE). Moreover, alcohol abstinence during follow-up was less common after RAH (18% vs. 45%, p <0.001). Most importantly, long-term mortality was higher in patients who developed RAH (39% vs. 21%, p = 0.026), and presenting with RAH independently predicted high mortality (HR: 1.55 [1.11-2.18]). CONCLUSIONS: RAH is common and has a more aggressive clinical course, including increased mortality. Patients surviving an episode of AH should undergo intense alcohol use disorder therapy to prevent RAH.

Prevalence and clinical impact of alcohol withdrawal syndrome in alcohol-associated hepatitis and the potential role of prophylaxis: a multinational, retrospective cohort study.

Background: The prevalence and impact of alcohol withdrawal syndrome (AWS) in patients with alcohol-associated hepatitis (AH) are unknown. In this study, we aimed to investigate the prevalence, predictors, management, and clinical impact of AWS in patients hospitalized with AH. Methods: A multinational, retrospective cohort study enrolling patients hospitalized with AH at 5 medical centres in Spain and in the USA was performed between January 1st, 2016 to January 31st, 2021. Data were retrospectively retrieved from electronic health records. Diagnosis of AWS was based on clinical criteria and use of sedatives to control AWS symptoms. The primary outcome was mortality. Multivariable models controlling for demographic variables and disease severity were performed to determine predictors of AWS (adjusted odds ratio [OR]) and the impact of AWS condition and management on clinical outcomes (adjusted hazard ratio [HR]). Findings: In total, 432 patients were included. The median MELD score at admission was 21.9 (18.3-27.3). The overall prevalence of AWS was 32%. Lower platelet levels (OR = 1.61, 95% CI 1.05-2.48) and previous history of AWS (OR = 2.09, 95% CI 1.31-3.33) were associated with a higher rate of incident AWS, whereas the use of prophylaxis decreased the risk (OR = 0.58, 95% CI 0.36-0.93). The use of intravenous benzodiazepines (HR = 2.18, 95% CI 1.02-4.64) and phenobarbital (HR = 2.99, 95% CI 1.07-8.37) for AWS treatment were independently associated with a higher mortality. The development of AWS increased the rate of infections (OR = 2.24, 95% CI 1.44-3.49), the need for mechanical ventilation (OR = 2.49, 95% CI 1.38-4.49), and ICU admission (OR = 1.96, 95% CI 1.19-3.23). Finally, AWS was associated with higher 28-day (HR = 2.31, 95% CI 1.40-3.82), 90-day (HR = 1.78, 95% CI 1.18-2.69), and 180-day mortality (HR = 1.54, 95% CI 1.06-2.24). Interpretation: AWS commonly occurs in patients hospitalized with AH and complicates the hospitalization course. Routine prophylaxis is associated with a lower prevalence of AWS. Prospective studies should determine diagnostic criteria and prophylaxis regimens for AWS management in patients with AH. Funding: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Prevalence and Treatment Outcomes of Arrhythmias in Patients with Single Ventricle Physiology over the Age of 40 Years.

Background: Arrhythmias are a well known complication in patients with single ventricle physiology (SVP). However, there is still a lack of data regarding arrhythmias in older patients. The aim of this study was to analyze arrhythmia type and frequency, treatment and recurrence rates in patients with SVP over the age of 40 years. Methods: Data was obtained retrospectively from clinical records. All patients > 40 years with SVP with arrhythmias between 2005 and 2018 were included in the study. Treatment was classified as medical, interventional (electrophysiological studies (EPS) in combination with catheter ablation) or direct current cardioversion (DCCV). Results: Altogether, 29 patients (11 female; mean 47.5 ± 4.6 years) with 85 arrhythmia episodes were identified. The median follow-up time was 6.3 years. Cavo-tricuspid (CTI) and non-CTI related intra-atrial reentrant tachycardia (IART) and atrial fibrillation (AF) were most common (48.2% and 37.6%, respectively). In total, 18 EPS/ablations were performed in 9 patients and 52 DCCVs in 20 patients. Acute success was 98% for DCCV and 72.2% for EPS/ablation. Recurrence rate was high (70% for DCCV and 55% for EPS). AT recurrences occurred after a median of 8 and 2.5 months, respectively. On multivariate analyses, age was the only risk factor for arrhythmia recurrence (HR 0.58, 95% C.I. 0.43−0.78, p < 0.0001). Pacemaker implantation was necessary in seven patients (AV block n = 4, sinus node dysfunction n = 3) and one patient received an ICD for secondary prophylaxis. Sudden death occurred in three patients. Conclusions: The most common arrhythmias in patients with SVP > 40 years are IART and AF. Arrhythmia recurrence following EPS or DCCV is frequent. Older age is an independent risk factor for arrhythmia recurrence.

Congenitally Corrected Transposition of the Great Arteries in Adults-A Contemporary Single Center Experience.

BACKGROUND: Congenitally corrected transposition of the great arteries (ccTGA) is a rare congenital heart defect (CHD). Contemporary data regarding its outcome in adults are scarce. METHODS: Retrospective, single-center study of all ccTGA patients over the age of 16 years treated at our center during the time period 2006-2018. Only patients with a biventricular circulation were included. The primary endpoint was all-cause mortality. RESULTS: Altogether, 96 patients (mean age 32.8 ± 16.0 years, female 50%) with ccTGA and a systemic right ventricle (SRV) were included in the study. An additional CHD was present in 81 patients (84.4%); most common were a ventricular septal defect (VSD) and a left ventricular outflow tract obstruction. Out of the whole cohort, 45 (46.9%) had already undergone cardiac surgery at baseline. During a median follow-up of 6.5 (IQR 2.8-12.7) years, the primary endpoint occurred in 10 patients (10.8%). Cause of death was cardiac in nine patients and suicide in one. Hospitalizations due to heart failure occurred in 48 patients (51.6%). Upon univariate Cox analysis, an NYHA class ≥III, severe tricuspid regurgitation, severe SRV systolic impairment, as well as a reduced left ventricular systolic function were predictors of the primary endpoint. Upon multivariable analysis, only NYHA class ≥ III (HR: 18.66, CI 95%: 3.01-115.80, p = 0.0017) and a reduced left ventricular systolic function (HR: 7.36, CI 95%: 1.18-45.99, p = 0.038) remained as independent predictors. CONCLUSIONS: Adults with ccTGA and an SRV are burdened with significant morbidity and mortality. Predictors for mortality are NYHA class and subpulmonary left ventricular function.

Complete Atrioventricular Septal Defects after the Age of 40 Years.

BACKGROUND: There is an increasing number of adults with complete atrioventricular septal defects (cAVSD). However, data regarding older adults are lacking. The aim of this study is to analyze the outcome of adults with cAVSD over the age of 40 years. METHODS: Patients with cAVSD who were ≥40 years of age at any point between 2005 until 2018 were included retrospectively. Data were retrieved from hospital records. The primary endpoint was a combination of death from any cause and unplanned hospitalizations due to cardiac reasons. RESULTS: 43 patients (60.5% female, mean age 43.7 ± 6.0 years, genetic syndrome 58.1%) were included. At begin of follow-up, the majority of patients (n = 41, 95.3%) was in New York Heart Association (NYHA) class I or II. Out of the whole cohort 26 (60.5%) had undergone cardiac surgery. At baseline, at least one extracardiac comorbidity was present in 40 patients (93.0%). Median follow-up was 1.7 years (IQR 0.3-4.6). On univariate Cox analysis, NYHA class at begin of follow-up (hazard ratio: 1.96, CI 95%: 1.04-3.72, p < 0.05) was the only predictor for the primary endpoint. CONCLUSIONS: Significant morbidity and mortality is present in cAVSD patients over the age of 40 years. NYHA class is predictive for a worse outcome.

Pulmonary Arterial Hypertension Associated with Congenital Heart Disease in Adults over the Age of 40 Years.

BACKGROUND: Pulmonary arterial hypertension associated with adult congenital heart disease (PAH-ACHD) leads to significant mortality at a young age. Risk factors for a negative outcome in older adults are lacking. METHODS: PAH-ACHD patients ≥ 40 years of age under active follow-up between January 2005 and December 2018 were included. Demographic data, as well as medical/surgical history, were retrieved from hospital records. The primary end-point was all-cause mortality. RESULTS: In total, 65 patients (67.7% female, mean age 45.19 ± 6.75 years) were included. Out of these, 46 (70.8%) had a shunt lesion, 12 (18.5%) had PAH associated with complex congenital heart defects, and 7 (10.8%) had segmental pulmonary hypertension due to major aorto-pulmonary collaterals. Down syndrome was present in 13 patients (20.0%). During a median follow-up of 4.2 years (IQR 1.2-7.5), 16 patients (24.6%) died. On univariate analysis, NT-proBNP (log), creatinine, and a previous history of ventricular arrhythmias were predictors of all-cause mortality. Upon multivariate analysis, NT-proBNP (log) (HR: 4.1, 95% CI: 1.2-14.4, p = 0.029) and creatinine (HR: 16.3, 95% CI: 2.2-118.7, p = 0.006) remained as independent predictors of all-cause mortality. CONCLUSIONS: PAH-ACHD patients over the age of 40 years are burdened with significant mortality, of which NT-proBNP and creatinine are independent predictors.

Patients with Single-Ventricle Physiology over the Age of 40 Years.

BACKGROUND: Single-ventricle physiology (SVP) is associated with significant morbidity and mortality at a young age. However, survival prospects have improved and risk factors for a negative outcome are well described in younger cohorts. Data regarding older adults is scarce. METHODS: In this study, SVP patients under active follow-up at our center who were ≥40 years of age at any point between January 2005 and December 2018 were included. Demographic data, as well as medical/surgical history were retrieved from hospital records. The primary end-point was all-cause mortality. RESULTS: Altogether, 49 patients (19 female (38.8%), mean age 49.2 ± 6.4 years) were included. Median follow-up time was 4.9 years (interquartile range (IQR): 1.8-8.5). Of these patients, 40 (81.6%) had undergone at least one cardiac surgery. The most common extracardiac comorbidities were thyroid dysfunction (n = 27, 55.1%) and renal disease (n = 15, 30.6%). During follow-up, 10 patients (20.4%) died. On univariate analysis, renal disease and liver cirrhosis were predictors of all-cause mortality. On multivariate analysis, only renal disease (hazard ratio (HR): 12.5, 95% confidence interval (CI): 1.5-106.3, p = 0.021) remained as an independent predictor. CONCLUSIONS: SVP patients ≥40 years of age are burdened with significant morbidity and mortality. Renal disease is an independent predictor of all-cause mortality.

Tetralogy of Fallot or Pulmonary Atresia with Ventricular Septal Defect after the Age of 40 Years: A Single Center Study.

Background: The population of adults with tetralogy of Fallot (TOF) or pulmonary atresia with ventricular septal defect (PA/VSD) is growing and aging. Data regarding older patients are scarce. Prognostic outcome parameters in adults with TOF or PA/VSD ≥ 40 years were studied. METHODS: This was a retrospective study of patients ≥ 40 years of age during the study period (January 2005-March 2018). Major adverse cardiac events (MACE) were a combined primary endpoint including death from any cause, prevented sudden cardiac death, pacemaker implantation, arrhythmia, and new-onset heart failure. Additionally, MACE II (secondary endpoint) was a combination of death from any cause and prevented sudden cardiac death. RESULTS: 184 (58.7% female, mean age 45.3 ± 7.2 years) patients were included (159 (86.4%) TOF and 25 (13.6%) PA/VSD). During a median follow-up of 3.1 years (IQR: 0.6-6.5), MACE occurred in 35 and MACE II in 13 patients. On multivariable analysis, New York Heart Association class [HR: 2.1, 95% CI: 1.2-3.6, p = 0.009] emerged as an independent predictor for MACE, and age at corrective surgery [HR: 13.2, 95% CI: 1.6-107.1, p = 0.016] for MACE II. CONCLUSIONS: Adults with TOF or PA/VSD ≥ 40 years are burdened with significant morbidity and mortality. New York Heart Association class and age at corrective surgery were independent predictors of outcome.

Direct oral anticoagulants in adults with congenital heart disease - a single centre study.

BACKGROUND: Direct oral anticoagulants (DOACs) have been proven to be safe and effective in patients with acquired heart disease. However, data regarding their use in adults with congenital heart disease (ACHD) is scarce. METHODS: All ACHD under DOAC were retrospectively identified. Bleeding and thromboembolic events were registered. CHADS2, CHA2DS2-VASc and HASBLED scores were calculated. Risk factors for bleeding and thromboembolic events were identified. RESULTS: 215 ACHD patients (111 female, 48.4 ±â€¯15.5 years) were included. CHD was severe in 44.2%, moderate in 23.7%, and simple in 32.1%. Indications for anticoagulation were: atrial arrhythmias (66.8%), cerebrovascular accidents (32.7%), pulmonary thromboembolism (3.7%), deep vein thrombosis (11.2%), atrial thrombi (6.5%), and Fontan circulation/TCPC (5.6%). Mean follow-up was 15.8 ±â€¯15.8 months. Nine patients suffered a major and eight a minor bleeding. Thromboembolic events occurred in two patients. The annual risk for bleeding was 3.1%/patient/year and for thromboembolic events 0.7%/patient/year. A CHADS2-Score >2, HASBLED >3, and renal disease were identified as risk factors for bleeding (minor and major bleeding) in a univariate analysis. In the multivariate analysis, renal disease remained as an independent predictor for bleeding (HR 6.13, CI [1.04-36.27], p < 0.05). It was also the only risk factor for major bleedings (HR 13.75, CI [2.60-72.54], p = 0.002). Risk factors for thromboembolic events were not identified. CONCLUSIONS: A low rate of thromboembolic events was observed in ACHD patients under DOAC therapy. Bleeding complications were not negligible. Special attention has to be paid to those patients with advanced renal failure.

Hemostatic abnormalities in adult patients with Marfan syndrome.

BACKGROUND: Aortic root ectasia might induce hemostatic disorders in patients with Marfan syndrome (MFS) via altered blood flow and rheology. The aim of this study was to explore the hemostasis in patients with MFS compared with healthy controls. METHODS: In this cross-sectional case-control study we included patients with verified MFS (n=51) and sex- and age-matched healthy controls (n=50). Main criteria were the aortic root in echocardiography and cardiac magnetic resonance imaging (MRI), and the coagulation status. RESULTS: When compared with healthy controls, patients with MFS showed significantly increased diameters of the aortic roots (43.0±7.72 vs. 28.8±3.74 mm, P<0.001) and aortic Z-scores (4.36±2.77 vs. 0.948±1.09, P<0.001), considerably higher values of Multiplate® tests (e.g., MP-ADP: 878.4±201.7 vs. 660.4±243.6 AU*min, P<0.001) and PFA-100® tests (PFA Col/ADP: 102.5±45.5 vs. 91.1±46.2 s, P<0.05), PTT (30.0±3.91 vs. 28.7±2.50 s, P<0.05) and D-dimers (0.488±0.665 vs. 0.254±0.099 mg/L, P<0.001). In MFS von Willebrand factor (VWF) activity (81.9%±41.8% vs. 106.3%±41.5%, P<0.05) and antigen (93.8%±43.9% vs. 118.8%±47.8%, P<0.05) and factor VIII activity (108.9%±29.6% vs. 126.7%±28.4%, P<0.05) were reduced. Significant positive correlations were found between aortic diameters and D-dimers (all P<0.05), as well as PFA Col/ADP (all P<0.01) in MFS patients. Factor VIII activity correlated significantly negatively with the diameter of the aortic root in MFS (r=-0.55, P<0.05). CONCLUSIONS: In conclusion, our study reveals hemostatic deviations in patients with MFS. Further studies are necessary to understand the causal relationship and the exact pathomechanism.

Value of Rotational Thromboelastometry and Impedance Aggregometry for Evaluating Coagulation Disorders in Patients With Cyanotic and Nongenetic Congenital Heart Disease.

Adults with cyanotic congenital heart diseases (CCHD) have a higher risk for bleeding, but also for thrombosis. Rotational thromboelastometry (RT), using tissue factor (EXTEM), a contact activator (INTEM) or cytochalasin (FIBTEM), assesses coagulation by determining the time to initiation of clotting (CT) and clot firmness (MCF) including platelet-fibrin-interaction. The aim of this study was to evaluate RT and whole blood impedance aggregometry (IA) in CCHD compared with a control group without chronic cyanosis (NCCHD). These were used to establish normal reference ranges. We prospectively included 124 patients (76 CCHD, 48 NCCHD). Mean oxygen saturation in CCHD was 81.5%, and 98% in NCCHD (p <0.001). Fifty-five CCHD and 1 NCCHD had pulmonary hypertension. Eisenmenger syndrome was present in 39 CCHD (51.3%). Hemoglobin, hematocrit, and reticulocyte levels were significantly higher in CCHD, and they also showed more thrombocytopenia. Platelet aggregation was under normal range in 89.5% of CCHD after triggering with ADP, in 85.5% after triggering with arachidonic acid (ASPI) and in 73.7% after TRAP-6. RT showed significantly longer clotting times and reduced clot firmness in both EXTEM and INTEM tests. FIBTEM-MCF was also significantly reduced. Moderate inverse correlation was found between platelet count and erythrocytes (r = -0.608, p <0.001). Significant correlations were found between platelet number and RT-parameters as well as with all IA parameters. In conclusion, according to RT and IA, CCHD present hypocoagulable disorders. No signs of hypercoagulability were found.

Non-cardiac comorbidities in adults with inherited and congenital heart disease: report from a single center experience of more than 800 consecutive patients.

BACKGROUND: As a result of improved surgical and therapeutical management, more than 90% of patients with congenital heart disease (CHD) reach adulthood. However, the natural course of CHD is complicated by noncardiac medical problems. Aim of the study was to evaluate noncardiac comorbidities in a contemporary cohort of adults with CHD (ACHD). METHODS: In a tertiary care center for ACHD, 821 consecutive patients, admitted to the outpatient clinic, were evaluated for clinically relevant noncardiac comorbidities. RESULTS: The consecutively included patients (age: range, 15-80 years; 56% female) represent all types and severity grades of acyanotic and cyanotic CHD. A considerable proportion of ACHD had significant noncardiac comorbidities, which have the potential to profoundly influence the natural course of the underlying disease. In 95.5%, relevant non-cardiac comorbidities were apparent, that could be related to 16 special medical fields as endocrinologic/metabolic disease, gastroenterology/hepatology, gynecology/obstetrics, angiology, orthopedics, neurology/psychiatry and others. Most frequently seen comorbidities were endocrine and metabolic disorders (43.97%). CONCLUSIONS: Non-cardiac comorbidities are increasingly common in ACHD. The data revealed non-cardiac comorbidities as they were presented in the cohort of ACHD seen in a tertiary center. The study proves that ACHD with significant non-cardiac comorbidities need multidisciplinary care by medical organ specialists, aside the congenital cardiologist, with a deep knowledge about congenital heart defects, the special effects of the organ disease on the particular heart defect and, how the heart defect may affect the course of the particular organ disease. The study may create the basis for the development of screening programs for comorbidities in ACHD as well as a multidisciplinary concept for diagnosis and treatment of concomitant disorders or for disease prevention. Particularly disease prevention may improve quality of life as well as the further fate of the affected patients.

Usefulness of Direct Oral Anticoagulants in Adult Congenital Heart Disease.

As thromboembolic events (TEE) are common in adults with congenital heart disease (ACHD), adequate oral anticoagulation for prophylaxis or treatment of TEE is important. Until now, mainly vitamin K antagonists have been used in these patients. The purpose of this study was to provide first data on the use of direct oral anticoagulants in ACHD. This prospective, observational, and longitudinal study included 102 consecutive ACHD, of whom 75 (37 women and 38 men; mean age 50 ± 13 years) could be analyzed. Most common CHD were pre-tricuspid shunts (n = 31; 41%), complex CHD (n = 16; 21%), left heart/aortic valve anomalies (n = 5; 6%), right-sided cardiac/pulmonary artery anomalies (n = 9; 13%), post-tricuspid shunts (n = 3; 4%), and others (n = 11; 15%). Five patients had cyanosis and 3 patients a Fontan circulation. Mean follow-up was 12 ± 11 months. Rivaroxaban was administered in 55 patients, apixaban in 13 and dabigatran in 7 patients for TEE prophylaxis in atrial arrhythmias (n = 57), stroke/transient ischemic attacks (n = 11), deep vein thrombosis (n = 4), pulmonary embolism (n = 1) and atrial thrombi (n = 3). Some patients had >1 indication for adequate oral anticoagulation. CHA2-DS2-VASc score was ≥ 2 in 23 (31%), and 9 (12%) had a HAS-BLED score ≥ 2. There were neither thrombotic or major bleeding events nor major side effects. In conclusion, direct oral anticoagulants appear to be safe and effective in ACHD. Long-term follow-up is needed to substantiate these findings.