Association of Cardiopulmonary Hemodynamics and Mortality in Veterans With Liver Cirrhosis: A Retrospective Cohort Study.

BACKGROUND: Portopulmonary hypertension (PoPH), associated with increased mortality, can limit treatment options for liver diseases. Data on the continuum of clinical risk related to cardiopulmonary hemodynamics in PoPH are lacking. METHODS AND RESULTS: As part of the United States national Veterans Affairs Clinical Assessment, Reporting, and Tracking database, we performed a retrospective cohort study of adults with cirrhosis undergoing right heart catheterization between October 1, 2017, and September 30, 2022. Pulmonary hypertension (mean pulmonary arterial pressure [mPAP] >20 mm Hg without PoPH) and PoPH (mPAP >20 mm Hg+pulmonary artery wedge pressure ≤15 mm Hg+pulmonary vascular resistance ≥3 WU) were defined by right heart catheterization hemodynamics. Multivariable Cox proportional hazards using natural splines for hemodynamic variables were used to evaluate the association between cardiopulmonary hemodynamics and mortality following right heart catheterization. A total of 4409 patients were included in the final analysis, predominantly men (96.3%), with a mean age of 68.5 years. Pulmonary hypertension and PoPH were observed in 71.6% and 10.2% of the cohort, respectively. Compared with a reference cardiac index of 2.5 L/min per m2, the hazard for mortality increased progressively with decreasing cardiac index, even after adjustment for mPAP and pulmonary vascular resistance. The minority of patients with PoPH (N=65, 14.5%) were prescribed pulmonary vasodilator therapy. CONCLUSIONS: These data suggest that pulmonary hypertension and PoPH are prevalent in veterans with chronic liver disease, but low use of targeted PoPH therapy persists. Cardiac function discriminated mortality risk across a wide range of mPAP and pulmonary vascular resistance values and may diagnose and clarify prognosis in this patient population.

The Pathophysiology(ies) of Heart Failure in Adults with Congenital Heart Disease.

There is a growing, aging population of adults with congenital heart disease (CHD) with an increasing incidence of heart failure. Unquestioning extrapolation of widely applicable definitions of heart failure and guidelines for managing heart failure in adults with acquired heart failure to adults with CHD can be problematic. A nuanced and flexible application of clinical judgment founded on a deep understanding of underlying pathophysiology is needed to most effectively apply the many recent advances in managing acquired heart failure to the care of adults with CHD.

Impact of Fontan Fenestration on Adverse Cardiovascular Outcomes: A Multicentre Study.

BACKGROUND: Fenestrating a Fontan baffle has been associated with improved perioperative outcomes in patients with univentricular hearts. However, longer-term potential adverse effects remain debated. We sought to assess the impact of a fenestrated Fontan baffle on adverse cardiovascular events including all-cause mortality, cardiac transplantation, atrial arrhythmias, and thromboemboli. METHODS: A multicentre North American retrospective cohort study was conducted on patients with total cavopulmonary connection Fontan baffle, with and without fenestration. All components of the composite outcome were independently adjudicated. Potential static and time-varying confounders were taken into consideration, along with competing risks. RESULTS: A total of 407 patients were followed for 10.4 (7.1-14.4) years; 70.0% had fenestration of their Fontan baffle. The fenestration spontaneously closed or was deliberately sealed in 79.9% of patients a median of 2.0 years after Fontan completion. In multivariable analysis in which a persistent fenestration was modelled as a time-dependent variable, an open fenestration did not confer a higher risk of the composite outcome (hazard ratio, 1.18; 95% confidence interval, 0.71-1.97; P = 0.521). In secondary analyses, an open fenestration was not significantly associated with components of the primary outcome: that is, mortality or transplantation, atrial arrhythmias, or thromboemboli. However, sensitivity analyses to assess the possible range of error resulting from imprecise dates for spontaneous fenestration closures could not rule out significant associations between an open fenestration and atrial arrhythmias or thromboemboli. CONCLUSIONS: In this multicentre study, no significant association was identified between an open fenestration in the Fontan baffle and major adverse cardiovascular events.

Associations of Liver Stiffness Measured by Ultrasound Shear-Wave Elastography With Portal Hypertension and Circulatory Failure in Individuals With Fontan Circulation.

BACKGROUND. The Fontan operation palliates single-ventricle congenital heart disease but causes hepatic congestion with associated progressive hepatic fibrosis. OBJECTIVE. The purpose of this study was to evaluate associations between liver stiffness measured using ultrasound (US) shear-wave elastography (SWE) in patients with Fontan palliation and the occurrence of portal hypertension and Fontan circulatory failure during follow-up. METHODS. This retrospective study included 119 individuals 10 years old or older (median age, 19.1 years; 61 female patients, 58 male patients) with Fontan circulation who underwent liver US with 2D SWE from January 1, 2015, to January 1, 2022, and had 1 year or more of clinical follow-up (unless experiencing earlier outcome-related events). Median liver stiffness from the initial US examination was documented. Varices, ascites, splenomegaly, and thrombocytopenia (VAST) scores (range, 0-4) were determined as a marker of portal hypertension on initial US examination and 1 year or more of follow-up imaging (US, CT, or MRI). Composite clinical outcome for Fontan circulatory failure (death, mechanical circulatory support, cardiac transplant, or unexpected Fontan circulation-related hospitalization) was assessed. Analysis included the Wilcoxon rank sum test, logistic regression analysis with stepwise variable selection, and ROC analysis. RESULTS. Median initial liver stiffness was 2.22 m/s. Median initial VAST score was 0 (IQR, 0-1); median follow-up VAST score was 1 (IQR, 0-2) (p = .004). Fontan circulatory failure occurred in 37 of 119 (31%) patients (median follow-up, 3.4 years). Initial liver stiffness was higher in patients with a follow-up VAST score of 1 or greater (2.37 m/s) than in those with a follow-up VAST score of 0 (2.08 m/s) (p = .005), and initial liver stiffness was higher in patients with (2.43 m/s) than without (2.10 m/s) Fontan circulatory failure during follow-up (p < .001). Initial liver stiffness was the only significant independent predictor of Fontan circulatory failure (OR = 3.76; p < .001); age, sex, Fontan operation type, dominant ventricular morphology, and initial VAST score were not independent predictors. Initial liver stiffness had an AUC of 0.70 (sensitivity, 79%; specificity, 57%; threshold, > 2.11 m/s) for predicting a follow-up VAST score of 1 or greater and an AUC of 0.74 (sensitivity, 84%; specificity, 52%; threshold, > 2.12 m/s) for predicting Fontan circulatory failure. CONCLUSION. In patients with Fontan circulation, increased initial liver stiffness was associated with portal hypertension and circulatory failure during follow-up, although it had moderate performance in predicting these outcomes. CLINICAL IMPACT. US SWE may play a role in post-Fontan surveillance, supporting tailored medical and surgical care.

Exercise Pathophysiology and Testing in Individuals With a Fontan Circulation.

The Fontan circulation, a surgical palliation for single-ventricle congenital heart disease, profoundly impacts the cardiopulmonary response to exercise. Reliant on passive pulmonary blood flow, the Fontan circulation has limited capacity to augment cardiac output as necessary to supply working muscles during exercise. Cardiopulmonary exercise testing (CPET) objectively assesses cardiorespiratory fitness and provides insight into the etiology of exercise intolerance. Furthermore, CPET variables, such as peak oxygen consumption and submaximal variables, have prognostic value and may be used as meaningful endpoints in research studies. CPET is also useful in clinical research applications to assess the effect of pharmacologic or other interventions. Medical therapies to improve exercise tolerance in individuals with a Fontan circulation, such as pulmonary vasodilators, may modestly improve peak oxygen consumption. Exercise training focused on aerobic fitness and lower extremity strength may have a more consistent and larger impact on these measures of aerobic fitness. CPET is a valuable diagnostic and prognostic tool for those with a Fontan circulation. Newer ancillary assessments, such as noninvasive peripheral venous pressure monitoring and cardiac output measurements, hold promise to provide a more nuanced insight into the underlying pathophysiology.

La circulation de Fontan, une solution chirurgicale palliative aux cardiopathies congénitales univentriculaires, a de profondes répercussions sur la réponse cardiorespiratoire à l'exercice physique. Puisqu'elle repose sur un flux sanguin pulmonaire passif, la circulation de Fontan présente une capacité limitée à accroître le débit cardiaque au besoin pour assurer l'approvisionnement des muscles durant l'effort physique. L'épreuve d'effort cardiorespiratoire (EECR) permet de mesurer la capacité cardiorespiratoire de manière objective et de mieux comprendre les causes de l'intolérance à l'effort. En outre, les variables mesurées lors de l'EECR, comme la consommation maximale d'oxygène (VO2) et les variables sous-maximales, ont une valeur pronostique et pourraient constituer des critères d'évaluation pertinents dans les travaux de recherche.L'EECR possède également des applications utiles en recherche clinique pour évaluer les effets des interventions pharmacologiques ou d'autre nature. Les traitements médicaux qui visent à améliorer la tolérance à l'effort chez les personnes ayant une circulation de Fontan, comme les vasodilatateurs pulmonaires, pourraient entraîner une modeste augmentation de la valeur maximale de VO2. L'entraînement physique axé sur la capacité aérobique et sur la force des membres inférieurs pourrait avoir un effet plus constant et important sur ces mesures de la capacité aérobique. L'EECR est un précieux outil diagnostique et pronostique pour l'évaluation des patients ayant une circulation de Fontan. Des méthodes d'évaluation complémentaires plus récentes, comme la surveillance non invasive de la pression veineuse périphérique et les mesures du débit cardiaque, sont des avenues prometteuses vers une compréhension plus nuancée des mécanismes physiopathologiques sous-jacents.

End-stage heart failure in congenitally corrected transposition of the great arteries: a multicentre study.

BACKGROUND AND AIMS: For patients with congenitally corrected transposition of the great arteries (ccTGA), factors associated with progression to end-stage congestive heart failure (CHF) remain largely unclear. METHODS: This multicentre, retrospective cohort study included adults with ccTGA seen at a congenital heart disease centre. Clinical data from initial and most recent visits were obtained. The composite primary outcome was mechanical circulatory support, heart transplantation, or death. RESULTS: From 558 patients (48% female, age at first visit 36 ± 14.2 years, median follow-up 8.7 years), the event rate of the primary outcome was 15.4 per 1000 person-years (11 mechanical circulatory support implantations, 12 transplantations, and 52 deaths). Patients experiencing the primary outcome were older and more likely to have a history of atrial arrhythmia. The primary outcome was highest in those with both moderate/severe right ventricular (RV) dysfunction and tricuspid regurgitation (n = 110, 31 events) and uncommon in those with mild/less RV dysfunction and tricuspid regurgitation (n = 181, 13 events, P < .001). Outcomes were not different based on anatomic complexity and history of tricuspid valve surgery or of subpulmonic obstruction. New CHF admission or ventricular arrhythmia was associated with the primary outcome. Individuals who underwent childhood surgery had more adverse outcomes than age- and sex-matched controls. Multivariable Cox regression analysis identified older age, prior CHF admission, and severe RV dysfunction as independent predictors for the primary outcome. CONCLUSIONS: Patients with ccTGA have variable deterioration to end-stage heart failure or death over time, commonly between their fifth and sixth decades. Predictors include arrhythmic and CHF events and severe RV dysfunction but not anatomy or need for tricuspid valve surgery.

Facility-Based and Virtual Cardiac Rehabilitation in Young Patients with Heart Disease During the COVID-19 Era.

Cardiac rehabilitation (CR) is an important tool for improving fitness and quality of life in those with heart disease (HD). Few pediatric centers use CR to care for these patients, and virtual CR is rarely used. In addition, it is unclear how the COVID-19 era has changed CR outcomes. This study assessed fitness improvements in young HD patients participating in both facility-based and virtual CR during the COVID-19 pandemic. This retrospective single-center cohort study included new patients who completed CR from March 2020 through July 2022. CR outcomes included physical, performance, and psychosocial measures. Comparison between serial testing was performed with a paired t test with P < 0.05 was considered significant. Data are reported as mean ± standard deviation. There were 47 patients (19 ± 7.3 years old; 49% male) who completed CR. Improvements were seen in peak oxygen consumption (VO2, 62.3 ± 16.1 v 71 ± 18.2% of predicted, p = 0.0007), 6-min walk (6 MW) distance (401 ± 163.8 v 480.7 ± 119.2 m, p = < 0.0001), sit to stand (16.2 ± 4.9 v 22.1 ± 6.6 repetitions; p = < 0.0001), Patient Health Questionnaire-9 (PHQ-9) (5.9 ± 4.3 v 4.4 ± 4.2; p = 0.002), and Physical Component Score (39.9 ± 10.1 v 44.9 ± 8.8; p = 0.002). Facility-based CR enrollees were less likely to complete CR than virtual patients (60%, 33/55 v 80%, 12/15; p = 0.005). Increases in peak VO2 (60 ± 15.3 v 70.2 ± 17.8% of predicted; p = 0.002) were seen among those that completed facility-based CR; this was not observed in the virtual group. Both groups demonstrated improvement in 6 MW distance, sit-to-stand repetitions, and sit-and-reach distance. Completion of a CR program resulted in fitness improvements during the COVID-19 era regardless of location, although peak VO2 improved more for the in-person group.

Associations Between Characteristics of Individuals With Fontan Circulation With Blood and Urine Biomarkers of Kidney Injury and Dysfunction.

Background Fontan circulation is associated with kidney injury and dysfunction, often unappreciated until Fontan circulatory failure. We hypothesized that cystatin C-estimated glomerular filtration rate (eGFR) would identify chronic kidney disease more frequently and that urine kidney injury biomarkers would be higher with declining Fontan physiological features. Methods and Results We enrolled 100 ambulatory individuals. Blood and urinary laboratory measurements were compared with demographics and clinically obtained data. Different eGFR equations were used for individuals aged ≥19 years and <19 years. Chronic kidney disease was defined as eGFR <90 mL/min per 1.73 m2. Median (25th-75th percentile) age was 19 (14-26) years, and 43% were female patients. Cystatin C eGFR detected chronic kidney disease (37%) in more patients than creatinine eGFR (11%). Cystatin C eGFR was positively associated, and skeletal muscle mass was negatively associated, with creatinine eGFR in both univariate (cystatin C eGFR ß=0.44±0.12, P=0.0006; skeletal muscle mass ß=-0.72±0.32, P=0.03) and multivariable analysis (cystatin C eGFR ß=0.43±0.12, P=0.0005; skeletal muscle mass ß=-0.69±0.29, P=0.02). Urine neutrophil gelatinase-associated lipocalin concentration correlated with Fontan pressure (r=0.28; P=0.04), ventricular end-diastolic pressure (r=0.28; P=0.04), and body fat mass (r=0.26; P=0.03). Conclusions Cystatin C eGFR identified more kidney dysfunction, likely attributable to creatinine eGFR being confounded by skeletal muscle mass. Elevated urine neutrophil gelatinase-associated lipocalin was associated with worse Fontan hemodynamics and higher percentage body fat, suggesting that higher venous pressure and higher adiposity are associated with ongoing kidney injury.

Single Center Experience With Durable Continuous Flow Single Ventricle Assist Device: A Viable Option in Fontan Circulatory Failure.

Ventricular assist devices are increasingly used for patients with single ventricle physiology. We describe the use of durable, continuous flow, single ventricular assist device (SVAD) therapy in Fontan circulatory failure patients. Retrospective, single-center review of patients with Fontan circulation implanted with a SVAD between 2017 and 2022. Patient characteristics and outcomes were obtained by chart review. Nine patients underwent SVAD implantation (median age 24 years). Most patients had a total cavopulmonary connection; one had an atriopulmonary Fontan. Five patients had a systemic right ventricle. SVAD was most often utilized as bridge to candidacy (67%). Eight patients had at least moderate systemic ventricular systolic dysfunction. SVAD support continued for a median of 65 days (longest duration, 1,105 days) and one patient remains on support at time of submission. Of five patients discharged home, median length of stay after SVAD was 24 days. Six patients were transplanted (median 96 days from SVAD). Two patients died from pretransplant multisystem organ failure before transplant. All transplanted patients remain alive (median time since transplant 593 days). Continuous flow SVAD therapy can be effective for patients with Fontan circulatory failure and systolic dysfunction. Further studies should investigate feasibility and optimal SVAD timing with more advanced Fontan associated end-organ dysfunction.

Isosorbide DiNitrate Effect on Hemodynamic Profile, Liver Stiffness, and Exercise Tolerance in Fontan Circulation (The NEET Clinical Trial).

After Fontan operation, decreased venous capacitance and venoconstriction are adaptive mechanisms to maintain venous return and cardiac output. The consequent higher venous pressure may adversely impact end-organ function, exercise capacity and result in worse clinical outcomes. This pilot study evaluated the safety and effect of isosorbide dinitrate (ISDN), a venodilator, on exercise capacity, peripheral venous pressure (PVP), and liver stiffness in patients with Fontan circulation. In this prospective single-arm trial, 15 individuals with Fontan circulation were evaluated at baseline and after 4 weeks of therapeutic treatment with ISDN. Primary aims were to assess the safety of ISDN and the effect on maximal exercise. We also aimed to evaluate the effect of ISDN on ultrasound-assessed liver stiffness, markers of submaximal exercise, and PVP at rest and peak exercise. Repeated measures t-tests were used to assess change in variables of interest in response to ISDN. Mean age was 23.5 ± 9.2 years (range 11.2-39.0 years), and 10/15 (67%) were male. There was no statistically significant change in peak VO2 (1401 ± 428 to 1428 ± 436 mL/min, p = 0.128), but VO2 at the anaerobic threshold increased (1087 ± 313 to 1115 ± 302 mL/min, p = 0.03). ISDN was also associated with a lower peak exercise PVP (22.5 ± 4.5 to 20.6 ± 3.0 mmHg, p = 0.015). Liver stiffness was lower with ISDN, though the difference was not statistically significant (2.3 ± 0.4 to 2.1 ± 0.5 m/s, p = 0.079). Of the patients completing the trial, mild headache was common (67%), but there were no major adverse events. Treatment with ISDN for 4 weeks is well-tolerated in patients with a Fontan circulation. ISDN is associated with an increase in VO2 at anaerobic threshold, lower peak PVP, and a trend toward lower liver stiffness. Larger, longer duration studies will be necessary to define the impact of ISDN on clinical outcomes in the Fontan circulation.Clinical Trial Registration: URL: https://clinicaltrials.gov . Unique identifier: NCT04297241.

Stable fitness during COVID-19: Results of serial testing in a cohort of youth with heart disease.

Background: Little is known about how sport and school restrictions early during the novel coronavirus 2019 (COVID-19) pandemic impacted exercise performance and body composition in youth with heart disease (HD). Methods: A retrospective chart review was performed on all patients with HD who had serial exercise testing and body composition via bioimpedance analysis performed within 12 months before and during the COVID-19 pandemic. Formal activity restriction was noted as present or absent. Analysis was performed with a paired t-test. Results: There were 33 patients (mean age 15.3 ± 3.4 years; 46% male) with serial testing completed (18 electrophysiologic diagnosis, 15 congenital HD). There was an increase in skeletal muscle mass (SMM) (24.1 ± 9.2-25.9 ± 9.1 kg, p < 0.0001), weight (58.7 ± 21.5-63.9 ± 22 kg, p < 0.0001), and body fat percentage (22.7 ± 9.4-24.7 ± 10.4%, p = 0.04). The results were similar when stratified by age <18 years old (n = 27) or by sex (male 16, female 17), consistent with typical pubertal changes in this predominantly adolescent population. Absolute peak VO2 increased, but this was due to somatic growth and aging as evidenced by no change in % of predicted peak VO2. There remained no difference in predicted peak VO2 when excluding patients with pre-existing activity restrictions (n = 12). Review of similar serial testing in 65 patients in the 3 years before the pandemic demonstrated equivalent findings. Conclusions: The COVID-19 pandemic and related lifestyle changes do not appear to have had substantial negative impacts on aerobic fitness or body composition in children and young adults with HD.

The impact of the COVID-19 pandemic on individuals with Fontan circulation: Focus on gaps in care.

Background: Gaps in subspecialty cardiology care could potentially delay identification and care for multi-organ complications common in patients with Fontan circulation. This study analyzed the frequency of gaps in care for individuals with Fontan circulation during the COVID-19 pandemic and associated demographic and clinical factors. Methods: This retrospective study evaluated individuals with Fontan circulation followed at our center since 2010. A gap in care was defined as an absence of any formal cardiology provider-patient contact (clinic visit or telehealth) for >15 months. Results: Over a third of 308 patients with Fontan circulation experienced at least one gap in care between 2010 and 2022, and 77 experienced a gap in care during the COVID-19 pandemic. Of this latter group, 27 (35%) had never experienced a prior gap in cardiology care until the pandemic. Those who experienced gaps in care during the pandemic were on average older (18.0 [IQR 9.6-25.6] vs. 14.2 [7.2-21.2] years, p = 0.01), more likely to be of Black/African American race (23.4% vs 7.4%, p = 0.001), and less likely to have a diagnosis of protein-losing enteropathy or plastic bronchitis (0% vs. 8.6%, p = 0.005). Those without a gap in care during the pandemic were more likely to have utilized telehealth visits (13% vs 3%, p = 0.02). Conclusion: Gaps in care are common and appear to have been exacerbated by the COVID-19 pandemic in those with a Fontan circulation. Such gaps are particularly common among African American and adult patients, and may potentially be mitigated by expanding telehealth access.

Cardiovascular Complications of Down Syndrome: Scoping Review and Expert Consensus.

Cardiovascular disease is a leading cause of morbidity and mortality in individuals with Down syndrome. Congenital heart disease is the most common cardiovascular condition in this group, present in up to 50% of people with Down syndrome and contributing to poor outcomes. Additional factors contributing to cardiovascular outcomes include pulmonary hypertension; coexistent pulmonary, endocrine, and metabolic diseases; and risk factors for atherosclerotic disease. Moreover, disparities in the cardiovascular care of people with Down syndrome compared with the general population, which vary across different geographies and health care systems, further contribute to cardiovascular mortality; this issue is often overlooked by the wider medical community. This review focuses on the diagnosis, prevalence, and management of cardiovascular disease encountered in people with Down syndrome and summarizes available evidence in 10 key areas relating to Down syndrome and cardiac disease, from prenatal diagnosis to disparities in care in areas of differing resource availability. All specialists and nonspecialist clinicians providing care for people with Down syndrome should be aware of best clinical practice in all aspects of care of this distinct population.

Pediatric and Congenital Cardiovascular Disease Research Challenges and Opportunities: JACC Review Topic of the Week.

The National Heart, Lung, and Blood Institute convened a workshop in August 2021 to identify opportunities in pediatric and congenital cardiovascular research that would improve outcomes for individuals with congenital heart disease across the lifespan. A subsidiary goal was to provide feedback on and visions for the Pediatric Heart Network. This paper summarizes several key research opportunities identified in the areas of: data quality, access, and sharing; aligning cardiovascular research with patient priorities (eg, neurodevelopmental and psychological impacts); integrating research within clinical care and supporting implementation into practice; leveraging creative study designs; and proactively enriching diversity of investigators, participants, and perspectives throughout the research process.

Long-Term Outcomes After Atrial Switch Operation for Transposition of the Great Arteries.

BACKGROUND: For patients with d-loop transposition of the great arteries (d-TGA) with a systemic right ventricle after an atrial switch operation, there is a need to identify risks for end-stage heart failure outcomes. OBJECTIVES: The authors aimed to determine factors associated with survival in a large cohort of such individuals. METHODS: This multicenter, retrospective cohort study included adults with d-TGA and prior atrial switch surgery seen at a congenital heart center. Clinical data from initial and most recent visits were obtained. The composite primary outcome was death, transplantation, or mechanical circulatory support (MCS). RESULTS: From 1,168 patients (38% female, age at first visit 29 ± 7.2 years) during a median 9.2 years of follow-up, 91 (8.8% per 10 person-years) met the outcome (66 deaths, 19 transplantations, 6 MCS). Patients experiencing sudden/arrhythmic death were younger than those dying of other causes (32.6 ± 6.4 years vs 42.4 ± 6.8 years; P < 0.001). There was a long duration between sentinel clinical events and end-stage heart failure. Age, atrial arrhythmia, pacemaker, biventricular enlargement, systolic dysfunction, and tricuspid regurgitation were all associated with the primary outcome. Independent 5-year predictors of primary outcome were prior ventricular arrhythmia, heart failure admission, complex anatomy, QRS duration >120 ms, and severe right ventricle dysfunction based on echocardiography. CONCLUSIONS: For most adults with d-TGA after atrial switch, progress to end-stage heart failure or death is slow. A simplified prediction score for 5-year adverse outcome is derived to help identify those at greatest risk.

Time in Therapeutic Range With Vitamin K Antagonists in Congenital Heart Disease: A Multicentre Study.

BACKGROUND: Vitamin K antagonists (VKAs) are frequently prescribed to patients with congenital heart disease (CHD) for atrial arrhythmias or Fontan palliation, but there is a paucity of data regarding time spent in the therapeutic range (TTR). We sought to determine the TTR in patients with CHD and atrial arrhythmias or Fontan palliation prescribed VKAs and explore associations with thromboembolic and bleeding events. METHODS: A multicentre North American cohort study was conducted on patients with CHD who received VKAs for sustained atrial arrhythmia or Fontan palliation. TTR was calculated using the Rosendaal linear interpolation method. Generalized estimating equations were used to explore factors associated with time outside the therapeutic range. RESULTS: A total of 567 patients, aged 33 ± 17 years, 56% female, received VKAs for 11.5 ± 8.4 years for atrial arrhythmias (63.0%) or Fontan palliation (58.0%). CHD was simple, moderate, and complex in 10.8%, 20.3%, and 69.0%, respectively. Site investigators perceived good control over international normalized ratio (INR) levels in most patients (75.3%), with no or minor compliance or adherence issues (85.6%). The mean TTR was 41.9% (95% confidence interval [CI], 39.0%-44.8%). Forty-seven (8.3%) and 34 (6.0%) patients had thromboembolic and bleeding events, respectively. Thromboembolic events were associated with a higher proportion of time below the therapeutic range (31.3% vs 19.1%, P = 0.003) and bleeding complications with a higher proportion of time above the therapeutic range (32.5% vs 19.5%, P = 0.006). CONCLUSIONS: Patients with CHD who receive VKAs spend < 42% of their time with INR levels in the therapeutic range, with repercussions regarding thromboembolic and bleeding complications.

Physical Frailty is Modifiable in Young Cardiac Rehabilitation Patients.

Frailty is a standardized, quantitative metric used to assess multisystem physiologic reserve and vulnerability to poor health outcomes. Cardiac rehabilitation (CR) positively impacts patient outcomes, including frailty, in adult cardiovascular disease (CVD); however, both the frailty paradigm and CR are understudied in pediatric CVD. This retrospective, single-center cohort study aimed to determine baseline composite frailty for pediatric-onset CVD patients and examine its change throughout CR using a proposed frailty assessment tool. Youth with pediatric-onset CVD participating in CR were stratified into five CVD diagnostic groups: post-heart transplant (HTx) (n = 34), post-ventricular assist device (VAD) (n = 12), single ventricle (n = 20) and biventricular (n = 29) congenital heart disease, and cardiomyopathy (n = 25), and frailty was assessed at baseline and every 30 days during CR. Post-HTx and post-VAD groups had significantly higher median frailty scores at baseline (6/10 and 5.75/10, respectively) driven by reduced strength, gait speed, and functional status. All groups except post-VAD displayed a significant absolute reduction in frailty from baseline to 120 days (HTx: - 3.5; VAD: - 3; SV CHD: - 1; BV CHD: - 1; CM: - 1.5), with similar median post-CR scores (1-3/10 in all groups). These improvements did not significantly correlate with number of CR sessions attended. This study established that frailty exhibits discriminatory utility across pediatric-onset CVD groups at baseline and is significantly modifiable over time. Improvements in frailty and other fitness metrics are likely due to a combination of post-operative recovery, post-diagnosis pharmacological and lifestyle changes, and CR. Further study of this frailty tool is needed to explore its prognostic utility.

Serial cardiac biomarker assessment in adults with congenital heart disease hospitalized for decompensated heart failure☆.

Background: Biomarkers are increasingly part of assessing and managing heart failure (HF) in adults with congenital heart disease (CHD). Objectives: To understand the response of cardiac biomarkers with therapy for acute decompensated heart failure (ADHF) and the relationship to prognosis after discharge in adults with CHD. Design: A prospective, observational cohort study with serial blood biomarker measurements. Settings: Single-center study in the inpatient setting with outpatient follow-up. Participants: Adults (≥18 years old) with CHD admitted with ADHF between August 1, 2019, and March 1, 2020. Exposure: We measured body mass, Kansas City Cardiomyopathy Questionnaire (KCCQ-12) score, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and high-sensitivity C-reactive protein (hsCRP) at enrollment, discharge, and 1st clinic follow-up visit; soluble suppression of tumorigenicity 2 (sST2) was measured at the first two time points. Measures: Univariate regression assessed the association between changes in weight, biomarkers, and changes in KCCQ-12 scores, between enrollment and discharge (Δ Hospitalization ) and between discharge and 1st clinical follow-up visit (Δ Post-discharge ). Wilcoxon rank-sum tests assessed the association between change in biomarkers, KCCQ-12 scores, and the composite outcome of cardiovascular death or rehospitalization for ADHF. Results: A total of 26 patients were enrolled. The median age was 51.9 years [IQR: 38.8, 61.2], 13 (54.2%) were women, and median hospital stay was 6.5 days [IQR: 4.0, 15.0] with an associated weight loss of 2.8 kg [IQR -5.1, -1.7]. All three cardiac biomarkers decreased during hospitalization with diuresis while KCCQ-12 scores improved; a greater decrease in sST2 was associated with an improved KCCQ-12 symptom frequency (SF) subdomain score (p = 0.012), but otherwise, there was no significant relationship between biomarkers and KCCQ-12 change. Change in hsCRP and NT-proBNP after discharge was not associated with the composite outcome (n = 8, vs. n = 16 who did not experience the outcome; Δ Post-discharge hsCRP +5.1 vs. -1.0 mg/l, p = 0.061; NT-proBNP +785.0 vs. +130.0 pg/ml, p = 0.220). Conclusions: Serial biomarker measurements respond to acute diuresis in adults with CHD hospitalized for ADHF. These results should motivate further research into the use of biomarkers to inform HF therapy in adults with CHD.

Abdominal CT and MRI Findings of Portal Hypertension in Children and Adults with Fontan Circulation.

Background Portal hypertension in the Fontan circulation is a function of elevated systemic venous pressure and liver fibrosis. Purpose To quantify the prevalence of radiologic evidence of portal hypertension and elevated VAST score (one point each for varices, ascites, splenomegaly, and thrombocytopenia) of 2 or greater in children and adults with Fontan circulation and to determine the association with hemodynamics and adverse outcomes. Materials and Methods This was a retrospective study of individuals with Fontan circulation who underwent abdominal MRI or CT for focal liver lesion surveillance between January 2012 and December 2019. Portal hypertension was defined as the presence of at least two of the following: varices, ascites, or splenomegaly. Fontan deterioration was defined as a composite of heart failure signs or symptoms requiring diuretic escalation, placement of a ventricular assist device, heart transplant, or death. Relationships between variables and the composite end point were assessed using univariable and multivariable logistic regression. Results A total of 123 patients (age range, 9-55 years; 32 children) were evaluated (median age, 23 years; IQR, 17-30 years; 63 male patients). Median time since diagnosis of Fontan circulation was 16 years (IQR, 12-23 years). Twenty-five of the 123 patients (20%) had radiologic evidence of portal hypertension, and 34 (28%) had a VAST score of 2 or greater. Fontan deterioration occurred in 25 of the 123 patients (20%); median follow-up duration was 0.4 year (IQR, 0.1-3.1 years). Compared with patients who had Fontan circulation without deterioration, patients with Fontan deterioration were more likely to have moderate or severe ventricular systolic dysfunction (P < .01), moderate or severe atrioventricular valve regurgitation (P < .01), higher Fontan pressure (P = .01), radiologic evidence of portal hypertension (P < .01), and VAST score of 2 or greater (P < .01). Conclusion Radiologic evidence of portal hypertension at abdominal imaging in children and adults with Fontan circulation was associated with higher venous pressures and an increased risk for Fontan deterioration. These characteristics may be used to identify patients who warrant comprehensive hemodynamic evaluation. © RSNA, 2022.