Diverse Right Ventricular Remodeling Evaluated by MRI and Prognosis in Eisenmenger Syndrome With Different Shunt Locations.

BACKGROUND: Congenital shunt location is related to Eisenmenger syndrome (ES) survival. Moreover, right ventricular (RV) remodeling is associated with poor survival in pulmonary hypertension. PURPOSE: To investigate RV remodeling using comprehensive magnetic resonance imaging (MRI) techniques and identify its relationship with prognosis in ES subgroups classified by shunt location. STUDY TYPE: Prospective observational study. POPULATION: Fifty-four adults with ES (16 with pre-tricuspid shunt and 38 with post-tricuspid shunt). FIELD STRENGTH/SEQUENCE: 3.0 T/cine MRI with balanced steady-state free precession sequence, late gadolinium enhancement with inversion recovery segmented gradient echo sequence and phase-sensitive reconstruction, and T1 mapping with modified Look-Locker inversion recovery sequence. ASSESSMENT: Demographics, clinical characteristics, hemodynamics, RV remodeling features (morphology, systolic function, RV-pulmonary artery (PA) coupling and myocardial fibrosis), and prognosis were compared between ES subgroups. The adverse endpoint was all-cause mortality or readmission for heart failure. STATISTICAL TESTS: The independent samples t-test, Fisher's exact test or Chi-squared test, and the Kaplan-Meier method were used. P < 0.05 was considered significant. RESULTS: Compared to patients with post-tricuspid shunt, patients with pre-tricuspid shunt were significantly older and had higher N-terminal pro-B-type natriuretic peptide concentrations and poorer exercise tolerance. Pre-tricuspid shunt showed significantly larger RV dimensions (end-diastolic volume index: 185.81 ± 37.49 vs. 98.20 ± 36.26 mL/m2 ), worse RV ejection fraction (23.54% ± 12.35% vs. 40.82% ± 10.77%), and RV-PA decoupling (0.35 ± 0.31 vs. 0.72 ± 0.29). Biventricular myocardial fibrosis was significantly more severe in pre-tricuspid shunt than post-tricuspid shunt (extracellular volume, left ventricle: 35.85% ± 2.58% vs. 29.10% ± 5.20%; RV free wall: 30.93% ± 5.65% vs. 26.75% ± 5.15%). In addition, pre-tricuspid shunt demonstrated a significantly increased risk of adverse endpoint (hazard ratio: 2.938, 95% confidence interval: 1.204-7.172). DATA CONCLUSION: ES with pre-tricuspid shunt might be a unique subtype with worse clinically decompensated RV remodeling and poor prognosis. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage: 5.

Detection and evaluation of myocardial fibrosis in Eisenmenger syndrome using cardiovascular magnetic resonance late gadolinium enhancement and T1 mapping.

BACKGROUND: Myocardial fibrosis is a common pathophysiological process involved in many cardiovascular diseases. However, limited prior studies suggested no association between focal myocardial fibrosis detected by cardiovascular magnetic resonance (CMR) late gadolinium enhancement (LGE) and disease severity in Eisenmenger syndrome (ES). This study aimed to explore potential associations between myocardial fibrosis evaluated by the CMR LGE and T1 mapping and risk stratification profiles including exercise tolerance, serum biomarkers, hemodynamics, and right ventricular (RV) function in these patients. METHODS: Forty-five adults with ES and 30 healthy subjects were included. All subjects underwent a contrast-enhanced 3T CMR. Focal replacement fibrosis was visualized on LGE images. The locations of LGE were recorded. After excluding LGE in ventricular insertion point (VIP), ES patients were divided into myocardial LGE-positive (LGE+) and LGE-negative (LGE-) subgroups. Regions of interest in the septal myocardium were manually contoured in the T1 mapping images to determine the diffuse myocardial fibrosis. The relationships between myocardial fibrosis and 6-min walk test (6MWT), N-terminal pro-brain natriuretic peptide (NT-pro BNP), hematocrit, mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance index (PVRI), RV/left ventricular end-systolic volume (RV/LV ESV), RV ejection fraction (RVEF), and risk stratification were analyzed. RESULTS: Myocardial LGE (excluding VIP) was common in ES (16/45, 35.6%), and often located in the septum (12/45, 26.7%). The clinical characteristics, hemodynamics, CMR morphology and function, and extracellular volume fraction (ECV) were similar in the LGE+ and LGE- groups (all P > 0.05). ECV was significantly higher in ES patients (28.6 ± 5.9% vs. 25.6 ± 2.2%, P < 0.05) and those with LGE- ES (28.3 ± 5.9% vs. 25.6 ± 2.2%, P < 0.05) than healthy controls. We found significant correlations between ECV and log NT-pro BNP, hematocrit, mPAP, PVRI, RV/LV ESV, and RVEF (all P < 0.05), and correlations trends between ECV and 6MWT (P = 0.06) in ES patients. An ECV threshold of 29.0% performed well in differentiating patients with high-risk ES from those with intermediate or low risk (area under curve 0.857, P < 0.001). CONCLUSIONS: Myocardial fibrosis is a common feature of ES. ECV may serve as an important imaging marker for ES disease severity.

Eisenmenger syndrome with left main compression syndrome: a case report.

BACKGROUND: Left main coronary artery disease secondary to pulmonary artery compression related to Eisenmenger syndrome is an under-suspected condition that can cause fatal outcomes if left untreated. It presents with typical angina but is frequently mistaken for pulmonary hypertension (PH) symptoms. It is now recognized as one of the few important causes of angina in PH. CASE PRESENTATION: A 37-year-old man with a history of unoperated atrial septal defect and Eisenmenger syndrome came to the outpatient department with a chief complaint of angina on exertion. Electrocardiogram showed regular sinus rhythm with right axis deviation, right ventricular hypertrophy, deep T-wave inversion in inferior and anterior leads suggestive of ischemia or strain, and incomplete right bundle branch block. Cardiac CT showed compression of the left main coronary artery due to a dilated main pulmonary artery. Therefore, this patient was diagnosed with Eisenmenger syndrome with left main compression due to dilated pulmonary artery. He was treated successfully with IVUS-guided stent implantation. The patient experienced marked improvement in regular activities, with no recurrence of angina symptoms. Angiography 3 months after the procedure revealed good patency of the stent, without significant stenosis. CONCLUSIONS: Left main coronary artery compression is a complication that should be suspected in patients with Eisenmenger syndrome presenting with angina symptoms. Non-invasive modalities are recommended for diagnostic evaluation, but the gold-standard technique remains coronary angiography. The best treatment is not well-established, with either myocardial revascularization or PH treatment, but a left main coronary artery stenting procedure is considered an ideal emergent treatment to provide a better quality of life for patients in this condition.

Evaluation of Macitentan in Patients With Eisenmenger Syndrome.

BACKGROUND: Eisenmenger syndrome describes congenital heart disease-associated severe pulmonary hypertension accompanied by right-to-left shunting. The multicenter, double-blind, randomized, placebo-controlled, 16-week, phase III MAESTRO study (Macitentan in Eisenmenger Syndrome to Restore Exercise Capacity) evaluated the efficacy and safety of the endothelin receptor antagonist macitentan in patients with Eisenmenger syndrome. METHODS: Patients with Eisenmenger syndrome aged ≥12 years and in World Health Organization functional class II-III were randomized 1:1 to placebo or macitentan 10 mg once daily for 16 weeks. Patients with complex cardiac defects, Down syndrome and background PAH therapy were eligible. The primary end point was change from baseline to week 16 in 6-minute walk distance. Secondary end points included change from baseline to week 16 in World Health Organization functional class. Exploratory end points included NT-proBNP (N-terminal pro-B-type natriuretic peptide) at end of treatment expressed as a percentage of baseline. In a hemodynamic substudy, exploratory end points included pulmonary vascular resistance index (PVRi) at week 16 as a percentage of baseline. RESULTS: Two hundred twenty six patients (macitentan n=114; placebo n=112) were randomized. At baseline, 60% of patients were in World Health Organization functional class II and 27% were receiving phosphodiesterase type-5 inhibitors. At week 16, the mean change from baseline in 6-minute walk distance was 18.3 m and 19.7 m in the macitentan and placebo groups (least-squares mean difference, -4.7 m; 95% confidence limit (CL), -22.8, 13.5; P=0.612). World Health Organization functional class improved from baseline to week 16 in 8.8% and 14.3% of patients in the macitentan and placebo groups (odds ratio, 0.53; 95% CL, 0.23, 1.24). NT-proBNP levels decreased with macitentan versus placebo (ratio of geometric means, 0.80; 95% CL, 0.68, 0.94). In the hemodynamic substudy (n=39 patients), macitentan decreased PVRi compared with placebo (ratio of geometric means, 0.87; 95% CL, 0.73, 1.03). The most common adverse events with macitentan versus placebo were headache (11.4 versus 4.5%) and upper respiratory tract infection (9.6 versus 6.3%); a hemoglobin decrease from baseline of ≥2 g/dL occurred in 36.0% versus 8.9% of patients. Five patients (3 macitentan; 2 placebo) prematurely discontinued treatment and 1 patient died (macitentan group). CONCLUSIONS: Macitentan did not show superiority over placebo on the primary end point of change from baseline to week 16 in exercise capacity in patients with Eisenmenger syndrome. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01743001.

Image diagnosis: Eisenmenger's syndrome in patients with simple congenital heart disease.

BACKGROUND: Early identification of congenital heart disease (CHD) allows detection of the pulmonary arteriopathy in an early stage, and timely shunt closure can permanently reverse pulmonary arterial hypertension (PAH). However, surgical correction is not recommended in patients with irreversible PAH. Herein we report our experience about Eisenmenger's syndrome in simple CHD. CASE PRESENTATION: From January 2017 to November 2018, a total of 8 CHD patients (3 ventricular septal defects (VSD), 2 atrial septal defects (ASD), and 3 patent ductus arteriosus (PDA), median age, 15.5 years [range, 3-18 years]) with PAH were detected by chest X-ray, electrocardiogram, transthoracic echocardiography (TTE), computed tomographic angiography (CTA) and cardiac catheterization. The median defect diameter, pulmonary artery pressure (PAP), pulmonary vascular resistance (PVR) were 16.5 mm (range, 3-30 mm), 75 mmHg (range, 60-86 mmHg), and 16 Woods units (range, 12-19 Woods units), respectively. Here, we report the representative cases of three types of simple CHD with irreversible PAH. The surgical correction was not performed in all patients who had fixed PAH and were referred to medical treatment. CONCLUSIONS: PAH in CHD can be reversed by early shunt closure, but this potential is lost beyond a certain point of no return. This article highlights the essence of enhancing the level of healthcare and services in Chinese rural areas. Failure to accurately and timely assess PAH will delay effective treatment past optimal treatment time, and even lead to death.

Transcatheter closure for patent ductus arteriosus in patients with Eisenmenger syndrome: to do or not?

BACKGROUND: Patent ductus arteriosus (PDA) complicated by Eisenmenger syndrome (ES) remains to be a major cause of morbidity and mortality worldwide. Giving increasing evidences of benefit from targeted therapies, ES patients once thought to be inoperable may have increasing options for management. This study aims to explore whether PDA in patients with ES can be treated with transcatheter closure (TCC). METHODS: Between August 2014 and July 2016, four of fifteen PDA-ES patients whose Qp/Qs improved significantly and Qp/Qs > 1.5 after acute vasodilator testing with 100% oxygen were selected to receive TCC and pulmonary vasodilator therapy. PAH-targeted drugs were prescribed before and after occlusion for all. Trial occlusion was performed before permanent closure. RESULTS: The first TCC failed after initiation of PAH-targeted drugs for 6 months in four patients. After the medication was adjusted and extended to 12 months, TCC was performed for all without hemodynamic intolerances during perioperative period. Pulmonary artery systolic pressure (PASP) was significantly decreased (≥ 40%) immediately after TCC. During a mean follow-up of 48 ± 14.70 months, there were a further decrease of PASPs in two patients, the other two showed improved pulmonary vascular resistance, WHO functional class and six-minute walking distance despite deteriorated PASP. CONCLUSION: Some selected PDA-ES patients might benefit from TCC and combined PAH-targeted drugs play a crucial role.

Aortopulmonary window in adults: A rare entity leading to Eisenmenger syndrome.

An aortopulmonary window (APW) is a rare congenital heart defect involving an abnormal communication between the ascending aorta and the pulmonary trunk with separate aortic and pulmonary valves. This defect accounts for 0.2% of all congenital cardiac anomalies and if left untreated can lead to Eisenmenger syndrome, severe pulmonary hypertension, heart failure, and poor survival. The authors herein present a case of APW type III with Eisenmenger syndrome in an adult patient whose initial complaint was cyanosis, and provide a thorough review of the literature of cases of APW with Eisenmenger syndrome that have survived into adulthood.

Utility of 4D Flow mapping in Eisenmenger syndrome with pulmonary atresia.

Management of patients with Eisenmenger syndrome with pulmonary atresia is challenging because of the complexity of the structure-function relationship of the components of the syndrome. Multi-modality imaging including cardiac magnetic resonance (CMR) 4D Flow offers unprecedented opportunities to unravel, at least in part, some of these components, and thus help in the management of these patients. In this study, we describe the use of these integrated methods with particular reference to CMR 4D Flow in a patient with Eisenmenger syndrome and pulmonary atresia and outline both the utility and the limitations. A comprehensive cardiac magnetic resonance (CMR) 4D Flow analysis was performed preoperatively and postoperatively, during peak systole, late systole, early diastole, and late diastole. The focus of the present study was to investigate the pattern of flow and dynamic changes at different levels of the aorta, as well as in the duct and the pulmonary arteries. Preoperatively, a right-handed helix and a vortex were observed in the dilated ascending aorta, and the duct flow was mainly dependent on reverse, upstream flow from the descending aorta, distal to the duct, during diastole, denoting low pulmonary vascular capacitance. Following repair, the flow in the ascending aorta and the descending aorta changed markedly. These changes included both timing and intensity of the right-handed helix, as well as the vortex in the ascending aorta. The significance of the observed changes in flow pattern and their influence on wall structure and function are discussed. Our study demonstrates the extremely powerful potential of CMR 4D Flow in the management of complex congenital anomalies.

Thoracic manifestation of Eisenmenger's syndrome in adult patients: a MDCT review.

Eisenmenger's syndrome (ES) is the most advanced form of pulmonary arterial hypertension (PAH) associated with congenital heart diseases (CHD). It is caused by simple or complex CHD with a large systemic-to-pulmonary shunt. When the pulmonary pressure exceeds the systemic pressure, the shunt reverses and central cyanosis appears. ES is a progressive and fatal condition, and it is accompanied by an increased risk of a range of potentially life-threatening complications. Patients with ES are both at risk for bleeding, due to damaged capillaries and high pressure, and for in situ pulmonary thrombosis, related to hyper-viscosity and slow blood flow in dilated pulmonary arteries. Moreover, the enlarged main pulmonary arteries and cardiac chambers may determine displacement or extrinsic compression on airways, pulmonary veins, coronary arteries, and other mediastinal structures. The clinical effects may be diverse, such as respiratory difficulties, localized pulmonary edema, cardiac dysfunction, or sudden death. Multidetector computed tomography (MDCT) allows to accurately assess in a single examination, pulmonary parenchyma and vessels, coronary artery origin, and heart chambers. The aim of this review was to illustrate the thoracic MDCT angiography findings and complications of adult patients with PAH-CHD and in particular of those with ES.

Left ventricular mass is preserved in patients with idiopathic pulmonary arterial hypertension and Eisenmenger's syndrome.

BACKGROUND: Left ventricular (LV) atrophic remodelling was described for chronic thromboembolic pulmonary hypertension (PH) but not in other forms of PH. We aimed to assess LV morphometric changes in idiopathic pulmonary arterial hypertension (IPAH) and Eisenmenger's syndrome(ES). METHODS: Fifteen patients with IPAH, 15 patients with ES and 15 healthy volunteers were included. Magnetic resonance was used to measure masses of LV, interventricular septum (IVS), LV free wall (LVFW), and LV end diastolic volume (LVEDV) indexed for body surface area. RESULTS: Between patients with IPAH, ES and controls no differences in LVmassindex (54.4[45.2-63.3] vs 58.7[41.5-106.1] vs 52.8[46.5-59.3], p=0.50), IVSmassindex (21.6[18.2-21.9)] vs 27.4[18.0-32.9] vs 20.7[18.2-23.2], p=0.18), and LVFWmassindex ([32.4[27.1-40.0] vs 36.7[30.9-62.1] vs 32.5[26.9-36.1], p=0.29) were found. LVEDVindex was lower in IPAH patients than in controls and in ES patients (54.9[46.9-58.5] vs 75.2[62.4-88.9] vs 73.5[62.1-77.5], p<0.001). In IPAH LVEDV but not LV mass correlated with pulmonary vascular resistance (r=-0.56, p=0.03) and cardiac output (r=0.59, p=0.02). CONCLUSIONS: LV mass is not reduced in patients with IPAH and with ES and is not affected by haemodynamic severity of PH. LVEDV is reduced in IPAH patients in proportion to reduced pulmonary flow but preserved in patients with ES, where reduced pulmonary flow to LV is compensated by right-to left shunt.

[The management of adult female patients with Eisenmenger syndrome and advanced pulmonary arterial hypertension treatment: single center experience and follow-up for 5 years]. / Eriskin kadin hastalarda Eisenmenger sendromuna yaklasim ve pulmoner arteriyel hipertansiyonda spesifik tedavi: tek merkeze ait klinik sonuçlar ve bes yillik izlem.

OBJECTIVES: Eisenmenger syndrome (ES) occurs as the most advanced form of pulmonary arterial hypertension (PAH) in patients with congenital heart disease. In this study, we aimed to evaluate the management of ES patients, follow-up and specific PAH treatment applying and clinical outcomes during 5 years. STUDY DESIGN: During the period of the month between May 2008 and 2013 ES female patients were included in the study and followed an average for 5 years. Clinical findings, brain natriuretic peptide levels, transthoracic and right heart catheterization findings, 6-min walking test distance were recorded. PAH specific treatment as bosentan, iloprost and sildenafil was given to patients according to guidelines. The patients were evaluated with 3 months intervals as requirement for hospitalization, combination treatment, and mortality. RESULTS: A total of 12 patients were included in the study. All of the patients were women, the mean age was 36.5. As prognostic echocardiographic data, the patients had high pulmonary artery pressure (109.81 ± 24.94 mmHg) related with increased right ventricular wall thickness, elevated right atrial pressure, severe pulmonary regurgitation in 40%, shortened pulmonary acceleration time, diminished myocardial tissue Doppler velocities of the left and right ventricles, increased right atrium area/left atrial area ratio (1.35 ± 0.40), lower right ventricular fractional area change. During the follow-up period of 5 years, a total of 16 events occurred. Combination treatment was required in 8 patients. CONCLUSION: Eisenmenger syndrome is a multi-system affecting disease and due to high morbidity and mortality risk patients with ES should be followed by specialized centers. PAH specific treatment improves the disease course and survival of patients.

Pseudo-subarachnoid haemorrhage: An unusual presentation of hyperviscosity syndrome.

Hyperviscosity syndrome can present with haematological, neurological or cardiovascular manifestations. The common differential diagnoses for severe headache and altered sensorium in a patient with Eisenmenger syndrome include brain abscess, meningitis, cortical venous thrombosis and subarachnoid haemorrhage (SAH). We report a patient with Eisenmenger syndrome with hyperviscosity, presenting as pseudo-SAH, which was successfully treated with phlebotomy.

Swyer-James-MacLeod Syndrome in a Patient with Eisenmenger Syndrome.

Swyer-James-MacLeod syndrome is characterized radiologically by hyperlucency in a single lung lobe, accompanied by reduced vascularity, alveolar hyperdistention, and air trapping, without bronchial airway obstruction. The most common congenital heart defect in childhood, ventricular septal defect, leads to irreversible pulmonary hypertension and Eisenmenger syndrome if not treated promptly. This case report presents a 25-year-old patient with Swyer-James-MacLeod syndrome and Eisenmenger syndrome. It is crucial to include Swyer-James-MacLeod syndrome in the differential diagnosis of patients with atypically distributed pulmonary emphysema and unilateral hyperlucency for early diagnosis and timely intervention.