Multi-modality imaging of the systemic right ventricle in congenital heart disease.

A comprehensive and structured imaging approach in the evaluation of the systemic right ventricle (sRV) in patients with complete transposition of the great arteries (TGA) after atrial switch procedure and congenitally corrected transposition of the great arteries (ccTGA) is a key for their optimal lifelong surveillance. Despite the improvements in cardiovascular imaging of adults with congenital heart disease (ACHD), the imaging of sRV remains an ongoing challenge due to its complex morphology and the difficulty in applying the existing knowledge for the systemic left ventricle. While cardiac magnetic resonance (CMR) is considered the gold standard imaging method, echocardiographic evaluation is primarily preferred in everyday clinical setting. Although qualitative assessment of its systolic function is primarily used, the introduction of advanced echocardiographic techniques, such as speckle tracking echocardiography (STE) and three-dimensional echocardiography (3DE), has provided new insights into the optimal assessment of the sRV. Standardized quantitative parameters remain to be elucidated, and morphometric and mechanistic studies are warranted to validate reference ranges for the sRV. This review highlights the challenges in the optimal evaluation of sRV and summarizes the available imaging tools. HIGHLIGHTS: CMR is the gold standard imaging method of sRV. Qualitative assessment of the systolic function of sRV is primarily used. Advanced echocardiographic techniques (STE and 3DE) provide optimal sRV assessment. Reference ranges for the sRV indices are warranted to be validated.

Arrhythmias in Patients with Congenital Heart Disease: An Ongoing Morbidity.

With the aging of congenital heart disease (CHD) patients, the burden of arrhythmias is expanding. Atrial arrhythmias, especially intra-atrial reentrant tachycardia and atrial fibrillation, are the most prevalent forms of arrhythmia. Managing comorbidities, such as obesity, using pharmacotherapy, including antiarrhythmics and anticoagulants, and ablation therapy has become the cornerstone of arrhythmia management. Ventricular tachycardias are also not rare; however, except for tetralogy of Fallot patients, recommendations for the use of implantable cardioverter defibrillators for primary prevention in other CHD patients are still not well established. Patients with CHD might also present with atrioventricular blockages because of their anatomy or following a surgical procedure. The scope of this article is to review the current knowledge and discuss the future directions regarding arrhythmia management in CHD patients.

Focused ultrasound neuromodulation of the spleen activates an anti-inflammatory response in humans.

Focused ultrasound stimulation (FUS) activates mechanosensitive ion channels and is emerging as a method of noninvasive neuromodulation. In preclinical studies, FUS of the spleen (sFUS) activates an anti-inflammatory neural pathway which suppresses acute and chronic inflammation. However, the relevance of sFUS for regulating inflammatory responses in humans is unknown. Here, we used a modified diagnostic ultrasound imaging system to target the spleen of healthy human subjects with 3 min of continuously swept or stationary focused pulsed ultrasound, delivered at three different energy levels within allowable safety exposure limits. Potential anti-inflammatory effects of sFUS were assessed by measuring sFUS-elicited changes in endotoxin-induced tumor necrosis factor (TNF) production in whole blood samples from insonified subjects. We found that stimulation with either continuously swept or focused pulsed ultrasound has an anti-inflammatory effect: sFUS lowers TNF production for >2 h, with TNF returning to baseline by 24 h following sFUS. This response is independent of anatomical target (i.e., spleen hilum or parenchyma) or ultrasound energy level. No clinical, biochemical, or hematological parameters are adversely impacted. This is the first demonstration that sFUS suppresses the normal inflammatory response in humans, with potential implications for noninvasive bioelectronic therapy of inflammatory disorders.

Association of Health Status Metrics with Clinical Outcomes in Patients with Adult Congenital Heart Disease and Atrial Arrhythmias.

The prognostic value of health status metrics in patients with adult congenital heart disease (ACHD) and atrial arrhythmias is unclear. In this retrospective cohort study of an ongoing national, multicenter registry (PROTECT-AR, NCT03854149), ACHD patients with atrial arrhythmias on apixaban are included. At baseline, health metrics were assessed using the physical component summary (PCS), the mental component summary (MCS) of the Short-Form-36 (SF-36) Health Survey, and the modified European Heart Rhythm Association (mEHRA) score. Patients were divided into groups according to their SF-36 PCS and MCS scores, using the normalized population mean of 50 on the PCS and MCS as a threshold. The primary outcome was the composite of mortality from any cause, major thromboembolic events, major/clinically relevant non-major bleedings, or hospitalizations. Multivariable Cox-regression analyses using clinically relevant parameters (age greater than 60 years, anatomic complexity, ejection fraction of the systemic ventricle, and CHA2DS2-VASc and HAS-BLED scores) were performed to examine the association of health metrics with the composite outcome. Over a median follow-up period of 20 months, the composite outcome occurred in 50 of 158 (32%) patients. The risk of the outcome was significantly higher in patients with SF-36 PCS ≤ 50 compared with those with PCS > 50 (adjusted hazard ratio (aHR), 1.98; 95% confidence interval [CI], 1.02−3.84; p = 0.04) after adjusting for possible confounders. The SF-36 MCS ≤ 50 was not associated with the outcome. The mEHRA score was incrementally associated with a higher risk of the composite outcome (aHR = 1.44 per 1 unit increase in score; 95% CI, 1.03−2.00; p = 0.03) in multivariable analysis. In ACHD patients with atrial arrhythmias, the SF-36 PCS ≤ 50 and mEHRA scores predicted an increased risk of adverse events.

The Adult Congenital Heart Disease Anatomic and Physiological Classification: Associations with Clinical Outcomes in Patients with Atrial Arrhythmias.

The implications of the adult congenital heart disease anatomic and physiological classification (AP-ACHD) for risk assessment have not been adequately studied. A retrospective cohort study was conducted using data from an ongoing national, multicentre registry of patients with ACHD and atrial arrhythmias (AA) receiving apixaban (PROTECT-AR study, NCT03854149). At enrollment, patients were stratified according to Anatomic class (AnatC, range I to III) and physiological stage (PhyS, range B to D). A follow-up was conducted between May 2019 and September 2021. The primary outcome was a composite of death from any cause, any major thromboembolic event, major or clinically relevant non-major bleeding, or hospitalization. Cox proportional-hazards regression modeling was used to evaluate the risks for the outcome among AP-ACHD classes. Over a median 20-month follow-up period, 47 of 157 (29.9%) ACHD patients with AA experienced the composite outcome. Adjusted hazard ratios (aHR) with 95% confidence intervals (CI) for the outcome in PhyS C and PhyS D were 1.79 (95% CI 0.69 to 4.67) and 8.15 (95% CI 1.52 to 43.59), respectively, as compared with PhyS B. The corresponding aHRs in AnatC II and AnatC III were 1.12 (95% CI 0.37 to 3.41) and 1.06 (95% CI 0.24 to 4.63), respectively, as compared with AnatC I. In conclusion, the PhyS component of the AP-ACHD classification was an independent predictor of net adverse clinical events among ACHD patients with AA.

Prediction Models and Scores in Adult Congenital Heart Disease.

Nowadays, most patients with congenital heart disease survive to adulthood due to advances in pediatric cardiac surgery but often present with various comorbidities and long-term complications, posing challenges in their management. The development and clinical use of risk scores for the prediction of morbidity and/or mortality in adults with congenital heart disease (ACHD) is fundamental in achieving optimal management for these patients, including appropriate follow-up frequency, treatment escalation, and timely referral for invasive procedures or heart transplantation. In comparison with other fields of cardiovascular medicine, there are relatively few studies that report prediction models developed in the ACHD population, given the small sample size, heterogeneity of the population, and relatively low event rate. Some studies report risk scores originally developed in pediatric congenital or non-congenital population, externally validated in ACHD with variable success. Available risk scores are designed to predict heart failure or arrhythmic events, all-cause mortality, post-intervention outcomes, infective endocarditis, or atherosclerosis-related cardiovascular disease in ACHD. A substantial number of these scores are derived from retrospective studies and are not internally or externally validated. Adequately validated risk scores can be invaluable in clinical practice and an important step towards personalized medicine. Multicenter collaboration, adequate study design, and the potential use of artificial intelligence are important elements in the effort to develop reliable risk scores for the ACHD population.

Hospitalizations in adult patients with congenital heart disease: an emerging challenge.

The vast majority of patients with congenital heart disease (CHD) survive into adulthood, but many face lifelong complications, which often result in a hospital admission. The increasing number of hospitalizations in adults with CHD (ACHD) poses a significant challenge for healthcare systems globally, especially as heart failure (HF) is becoming increasingly common in this population and is the leading cause of morbidity and mortality. Besides HF, other major contributors to this increase in admission volume are hospitalizations related to mild lesions, comorbidities and pregnancies. Ιn-hospital mortality ranges between 0.8 and 6.1%, while hospitalizations related to HF predict medium-term mortality in ACHD population. Understanding the predictors of hospitalization and in-hospital mortality is, therefore, important for ACHD healthcare providers, who should identify patients at risk that require escalation of treatment and/or close monitoring. This article reviews the available literature on hospitalization patterns in ACHD patients, with a focus on HF-related hospital admissions and specific diagnostic subgroups.

Rationale and design of a prospective, observational, multicentre study on the safety and efficacy of apixaban for the prevention of thromboembolism in adults with congenital heart disease and atrial arrhythmias: the PROTECT-AR study.

INTRODUCTION: The risk for stroke in adults with congenital heart disease (ACHD) is increased, especially in the setting of commonly ensuing atrial arrhythmias (AA), namely atrial fibrillation, atrial flutter or intra-atrial re-entrant tachycardia. Data are limited regarding treatment with non-vitamin K oral anticoagulants in long-term studies involving patients with ACHD and AA. METHODS AND ANALYSIS: PReventiOn of ThromboEmbolism in Adults with Congenital HearΤ disease and Atrial aRrhythmias is a prospective, multicenter, single-arm, non-interventional cohort study designed to investigate the safety and efficacy of apixaban for the prevention of thromboembolism in ACHD with AA in a 'real-world' setting. Eligible patients will be evaluated by the means of available registries and clinical counter. The study aims to accumulate approximately 500 patient-years of exposure to apixaban as part of routine care. Enrolment will take place at four ACHD centres in Greece. The first patient was enrolled in July 2019. The primary efficacy endpoint is a composite of stroke, systemic or pulmonary embolism and intracardiac thrombosis. The primary safety endpoint is major bleeding, according to the International Society on Thrombosis and Haemostasis bleeding criteria. ETHICS AND DISSEMINATION: The study protocol has been approved by the institutional review board/independent ethics committee at each site prior to study commencement. All patients will provide written informed consent. Results will be disseminated at scientific meetings and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03854149; Pre-results.

Hospitalisations for heart failure predict mortality in pulmonary hypertension related to congenital heart disease.

OBJECTIVE: Despite the progress in the management of patients with adult congenital heart disease (ACHD), a significant proportion of patients still develop pulmonary hypertension (PH). We aimed to highlight the rate of the complications in PH-ACHD and the predicting factors of cumulative mortality risk in this population. METHODS: Data were obtained from the cohort of the national registry of ACHD in Greece from February 2012 until January 2018. RESULTS: Overall, 65 patients receiving PH-specific therapy were included (mean age 46.1±14.4 years, 64.6% females). Heavily symptomatic (New York Heart Association (NYHA) class III/IV) were 53.8% of patients. The majority received monotherapy, while combination therapy was administered in 41.5% of patients. Cardiac arrhythmia was reported in 30.8%, endocarditis in 1.5%, stroke in 4.6%, pulmonary arterial thrombosis in 6.2%, haemoptysis in 3.1% and hospitalisation due to heart failure (HF) in 23.1%. Over a median follow-up of 3 years (range 1-6), 12 (18.5%) patients died. On univariate Cox regression analysis history of HF hospitalisation emerged as a strong predictor of mortality (HR 8.91, 95% CI 2.64 to 30.02, p<0.001), which remained significant after adjustment for age and for NYHA functional class. CONCLUSIONS: Long-term complications are common among patients with PH-ACHD. Hospitalisations for HF predict mortality and should be considered in the risk stratification of this population.

How to evaluate patients with congenital heart disease-related pulmonary arterial hypertension.

INTRODUCTION: Patients with congenital heart disease (CHD), who develop pulmonary arterial hypertension (PAH), live longer, and have better quality of life compared to the past due to PAH-specific therapy and improved tertiary care. Areas covered: Clinical examination, objective assessment of functional capacity, natriuretic peptide levels, cardiac imaging, and hemodynamics all play a pivotal role in the evaluation, general care, and management of PAH-specific therapy. This review discusses the epidemiology and pathophysiology of PAH-CHD and provides hints for the optimal evaluation of these patients. Expert commentary: Further research should be performed in the field of PAH-CHD, as there are many of areas lacking evidence that should be addressed in the future. Networking, especially among the tertiary expert centers, could play a key role in this direction.