Pregnancy in Congenital Heart Disease, Complicated by Pulmonary Arterial Hypertension-A Challenging Issue for the Pregnant Woman, the Foetus, and Healthcare Professionals.

Background and Objectives: Pregnancy and delivery in patients with congenital heart disease (CHD) and pulmonary arterial hypertension (PAH) carry a very high risk for maternal and foetal complications and are contraindicated according to the guidelines. In the last decades, when an available modern PAH-targeted medication therapy and a new management concept improved patients' well-being and survival, some PAH-CHD females decided to conceive. Of note, despite advanced treatment and modern healthcare system possibilities, dealing with pregnancy in a diverse PAH-CHD population is still challenging. The study aimed to share our experience with PAH-CHD pregnancies and discuss the risk assessment and current management of these patients with the combination of two rare diseases. Materials and Methods: The retrospective search of pulmonary hypertension and adult CHD registries in our hospital was performed, selecting all patients with CHD and PAH who conceived pregnancy from 2013 to 2021. Baseline demographic, clinical, and functional characteristics and clinical outcomes were collected. Results: Thirteen pregnancies in eight patients with PAH-CHD resulted in seven live births, three miscarriages, and three terminations. Five women were diagnosed with Eisenmenger syndrome (ES) and three with residual PAH after CHD repair. Before pregnancy, half of them were in WHO functional class III. Seven (87.5%) patients received targeted PAH treatment with sildenafil during pregnancy. In addition, the two most severe cases were administered with iloprost during peripartum. Three ES patients delivered preterm by Caesarean section under general anaesthesia. No neonatal mortality was reported. Maternal complications were observed in half of our cases. One patient died 12 days after the delivery in another hospital due to deterioration of heart failure. Conclusions: On the basis of our clinical experience, we conclude that pregnancy and delivery carry a high risk for maternal complications and should be avoided in women with PAH-CHD. The individualised approach of multidisciplinary care and appropriate monitoring are mandatory in reducing the risk of adverse outcomes.

Two Novel Variants in Genes of Arrhythmogenic Right Ventricular Cardiomyopathy - a Case Report.

SUMMARY BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heritable cardiomyopathy, characterized by fibrofatty replacement of myocytes in the right ventricular, left ventricular or both ventricles. It is caused by pathogenic variants of genes encoding desmosomal (JUP, DSP, PKP2, DSG2, DSC2) and non-desmosomal proteins, and is one of the most common causes of sudden cardiac death in young athletes. Therefore, early identification, correct prevention and treatment can prevent adverse outcomes. CASE REPORT: Our case presents a 65-years-old man with recurrent ventricular tachycardia. The ischemic cause was the first to rule out. Echocardiography revealed right ventricular structural and functional abnormalities. After suspicion of ARVC, magnetic resonance imaging was performed showing reduced right ventricular ejection fraction with local aneurysms, structural changes ir the right and left myocardium. Subsequently performed genetic testing identified a novel ARVC likely pathogenic variant in DSC2 gene and variant of uncertain significance in RYR2 gene. CONCLUSIONS: Diagnostic evaluation of ARVC is challenging and requires multidisciplinary team collaboration. Further functional tests for elucidation of the clinical significance of the two novel variants of ARVC-associated genes could be suggested.

Medical treatment of pulmonary hypertension in adults with congenital heart disease: updated and extended results from the International COMPERA-CHD Registry.

BACKGROUND: Pulmonary arterial hypertension (PAH) is common in congenital heart disease (CHD). Because clinical-trial data on PAH associated with CHD (PAH-CHD) remain limited, registry data on the long-term course are essential. This analysis aimed to update information from the COMPERA-CHD registry on management strategies based on real-world data. METHODS: The prospective international pulmonary hypertension registry COMPERA has since 2007 enrolled more than 10,000 patients. COMPERA-CHD is a sub-registry for patients with PAH-CHD. RESULTS: A total of 769 patients with PAH-CHD from 62 specialized centers in 12 countries were included into COMPERA-CHD from January 2007 through September 2020. At the last follow-up in 09/2020, patients [mean age 45.3±16.8 years; 512 (66%) female] had either post-tricuspid shunts (n=359; 46.7%), pre-tricuspid shunts (n=249; 32.4%), complex CHD (n=132; 17.2%), congenital left heart or aortic valve or aortic disease (n=9; 1.3%), or miscellaneous CHD (n=20; 2.6%). The mean 6-minute walking distance was 369±121 m, and 28.2%, 56.0%, and 3.8% were in WHO functional class I/II, III or IV, respectively (12.0% unknown). Compared with the previously published COMPERA-CHD data, after 21 months of follow-up, the number of included PAH-CHD patients increased by 91 (13.4%). Within this group the number of Eisenmenger patients rose by 39 (16.3%), the number of "Non-Eisenmenger PAH" patients by 45 (26.9%). Currently, among the 674 patients from the PAH-CHD group with at least one follow-up, 450 (66.8%) received endothelin receptor antagonists (ERA), 416 (61.7%) PDE-5 inhibitors, 85 (12.6%) prostacyclin analogues, and 36 (5.3%) the sGC stimulator riociguat. While at first inclusion in the COMPERA-CHD registry, treatment was predominantly monotherapy (69.3%), this has shifted to favoring combination therapy in the current group (53%). For the first time, the nature, frequency, and treatment of significant comorbidities requiring supportive care and medication are described. CONCLUSIONS: Analyzing "real life data" from the international COMPERA-CHD registry, we present a comprehensive overview about current management modalities and treatment concepts in PAH-CHD. There was an trend towards more aggressive treatment strategies and combination therapies. In the future, particular attention must be directed to the "Non-Eisenmenger PAH" group and to patients with complex CHD, including Fontan patients. TRIAL REGISTRATION: www.clinicaltrials.gov, study identifier: Clinicaltrials.gov NCT01347216.

Residual Pulmonary Hypertension more than 20 Years after Repair of Shunt Lesions.

Background and Objectives: After successful surgical repair of a congenital shunt lesion, pulmonary hypertension (PH) often disappears. However, PH can persist long-term after the closure. This study aimed to assess the prevalence of PH long-term after surgical repair of congenital heart disease (CHD), and to evaluate the outcomes and preoperative factors related to residual PH. Materials and Methods: In this retrospective cohort study, we reviewed patients who underwent right heart catheterisation in Vilnius University Hospital Santaros Klinikos during the period of 1985-2007. Among 4118 right heart catheterisations performed, 160 patients underwent congenital systemic-to-pulmonary shunt repair at a young age (<18 years) and had pre-operative PH. Half of the patients were foreigners whose follow-up data were unavailable. Eventually, 88 patients with available follow-up data were included in this study. Results: The median age at diagnosis of CHD with PH was 0.8 (0.6-3.0) and 1.1 (0.6-3.9) years at surgery (50% females). Residual PH was assessed 9.5 years after surgery and observed in 30.7% (n = 27) of the patients. It was associated with having more than one shunt (44.4% (n = 12), p = 0.016) and higher median pulmonary vascular resistance (3.4 (2.5-6.5) vs. 2.2 (1.0-3.7), p = 0.035) at baseline. After a median follow-up of 21 (15-24) years, 9.1% of the patients were deceased. Kaplan-Meier survival analysis revealed significantly higher mortality in the residual PH group (p = 0.035). Conclusions: Residual PH affects a significant proportion of patients after surgical repair of a shunt lesion and is associated with worse long-term outcome.

Insights to correlations and discrepancies between impaired lung function and heart failure in Eisenmenger patients.

Impaired lung function and spirometric signs of airway obstruction without common risk factors for chronic obstructive pulmonary disease could be found in patients with Eisenmenger syndrome. This study aimed to analyse the association between lung function parameters and disease severity (including heart failure markers, associated congenital heart defect) as well as the possible reasons for airflow obstruction in Eisenmenger syndrome. The data of 25 patients with Eisenmenger syndrome were retrospectively evaluated. The patients were divided into groups according to airflow obstruction and a type of congenital heart defect. Airflow obstruction was found in nearly third (32%) of our cases and was associated with older age and worse survival. No relation was found between airway obstruction, B-type natriuretic peptide level, complexity of congenital heart defect and bronchial compression. Most of the patients (88%) had gas diffusion abnormalities. A weak negative correlation was noticed between gas diffusion (diffusing capacity of the lung for carbon monoxide) and B-type natriuretic peptide level (r = -0.437, p = 0.033). Increased residual volume was associated with higher mortality (p = 0.047 and p = 0.021, respectively). A link between B-type natriuretic peptide and lung diffusion, but not airway obstruction, was found. Further research and larger multicentre studies are needed to evaluate the importance of pulmonary function parameters and mechanisms of airflow obstruction in Eisenmenger syndrome.

Electrocardiographic changes during therapeutic hypothermia: observational data from a single centre.

BACKGROUND: Therapeutic hypothermia is recommended to reduce the risk of hypoxic brain damage and improve short-term survival after cardiac arrest. It also temporarily affects the cardiac conduction system. The aim of this study was to evaluate electrocardiographic changes during therapeutic hypothermia and their impact on the outcome. MATERIALS AND METHODS: This retrospective analysis involved 26 patients who underwent therapeutic hypothermia after cardiac arrest in Vilnius University Hospital Santaros Klinikos from 2011 to 2015. RESULTS: During cooling, a significant reduction in the heart rate (p = 0.013), shortening of QRS complex duration (p = 0.041), and prolongation of the QTc interval (p < 0.001) were observed. During the cooling period, five patients had subtle Osborn waves, which disappeared after rewarming. The association between electrocardiographic changes during cooling and unfavourable neurological outcome or in-hospital mortality was non-significant. CONCLUSIONS: Therapeutic hypothermia after cardiac arrest causes reversible electrocardiographic changes that do not increase the risk of in-hospital mortality or unfavourable neurological outcomes.