Waitlist and post-transplant outcomes for eisenmenger syndrome: A comparison of transplant strategies.

BACKGROUND: End-stage Eisenmenger syndrome (ES) due to unrepaired atrial septal defect (ASD) or ventricular septal defect (VSD) is an indication for lung transplantation (LTx) or heart-lung transplantation (HLTx). Limited evidence exists as to the optimal transplant strategy for this unique population. AIM: To describe waitlist characteristics and post-transplant outcomes in patients with ES-ASD or ES-VSD. METHODS: Using the ISHLT Registry, data were extracted for all ES-ASD or ES-VSD patients who underwent transplantation between 1987 and 2018. Additional data were sought for patients listed for LTx or HLTx in the OPTN Registry during the same period. Early era was defined as 1987-2004, and current era was defined as 2005-2018. RESULTS: In the current era, patients with ES-ASD or ES-VSD represented a lessening proportion of all LTx and HLTx. Compared to LTx for other indications, the odds of transplantation were significantly less for both ES-ASD 0.18 [0.07-0.50] and ES-VSD 0.03 [0.004-0.22]. In the early era, an equivalent survival was observed for ES-ASD who underwent HLTx versus LTx (p = 0.47), and superior survival for ES-VSD (p = 0.015). In contrast, ES-ASD patients who underwent LTx from the current era displayed better survival compared with HLTx, 10-year survival 52% vs 30% p = 0.036. Similar survival were observed for ES-VSD for both transplant strategies (p = 0.68). CONCLUSION: LTx shows superior survival outcomes in the current era for ES ASD patients, and equivalent outcomes for ES-VSD. In the current era, ES-ASD or ES-VSD patients were less likely to be transplanted than other candidates for LTx.

Determinants of Sudden Cardiac Death in Adult Patients With Eisenmenger Syndrome.

Background Patients with Eisenmenger syndrome are known to have a high incidence of sudden cardiac death (SCD), yet the underlying causes are not well understood. We sought to define the predictors of SCD in this population. Methods and Results A retrospective analysis of all patients with Eisenmenger syndrome from 2 large tertiary referral centers was performed. ECGs, prolonged ambulatory recordings, echocardiograms, and clinical histories were reviewed; and the cause of death was identified. A total of 246 patients (85 [34.6%] men) with a mean age of 37.3 (±14.2) years were followed up for a median of 7 years. Over the study period, 136 patients died, with 40 experiencing SCD and 74 experiencing cardiac death (sudden and nonsudden). Age, atrial fibrillation, prolonged QRS duration, complete heart block, right atrial enlargement, right bundle branch block, increased right atrial pressure, impaired biventricular function, and the presence of a pacemaker were associated with increased risk of SCD, whereas advanced pulmonary hypertension therapies were protective. Atrial fibrillation (11.45-fold increased risk; P<0.001) and QRS duration ≥120 ms (2.06-fold increased risk; P=0.034) remained significant predictors of SCD in the multivariate analysis, whereas advanced pulmonary hypertension therapies were strongly protective against SCD (P<0.001). Conclusions Atrial arrhythmias, impaired ventricular function, and conduction system disease were associated with increased risk of SCD in this cohort of patients with Eisenmenger syndrome, providing an opportunity for early risk stratification and potential intervention. Clinical heart failure symptoms (New York Heart Association class ≥II) were predictive of increased mortality but not of SCD, suggesting a potential arrhythmic cause behind SCD.

Outcome after heart-lung or lung transplantation in patients with Eisenmenger syndrome.

OBJECTIVE: The optimal timing for transplantation is unclear in patients with Eisenmenger syndrome (ES). We investigated post-transplantation survival and transplantation-specific morbidity after heart-lung transplantation (HLTx) or lung transplantation (LTx) in a cohort of Nordic patients with ES to aid decision-making for scheduling transplantation. METHODS: We performed a retrospective, descriptive, population-based study of patients with ES who underwent transplantation from 1985 to 2012. RESULTS: Among 714 patients with ES in the Nordic region, 63 (9%) underwent transplantation. The median age at transplantation was 31.9 (IQR 21.1-42.3) years. Within 30 days after transplantation, seven patients (11%) died. The median survival was 12.0 (95% CI 7.6 to 16.4) years and the overall 1-year, 5-year, 10-year and 15-year survival rates were 84.1%, 69.7%, 55.8% and 40.6%, respectively. For patients alive 1 year post-transplantation, the median conditional survival was 14.8 years (95% CI 8.0 to 21.8), with 5-year, 10-year and 15-year survival rates of 83.3%, 67.2% and 50.0%, respectively. There was no difference in median survival after HLTx (n=57) and LTx (n=6) (14.9 vs 10.6 years, p=0.718). Median cardiac allograft vasculopathy, bronchiolitis obliterans syndrome and dialysis/kidney transplantation-free survival rates were 11.2 (95% CI 7.8 to 14.6), 6.9 (95% CI 2.6 to 11.1) and 11.2 (95% CI 8.8 to 13.7) years, respectively. The leading causes of death after the perioperative period were infection (36.7%), bronchiolitis obliterans syndrome (23.3%) and heart failure (13.3%). CONCLUSIONS: This study shows that satisfactory post-transplantation survival, comparable with contemporary HTx and LTx data, without severe comorbidities such as cardiac allograft vasculopathy, bronchiolitis obliterans syndrome and dialysis, is achievable in patients with ES, with a conditional survival of nearly 15 years.

Outcome of pregnancies in women with pulmonary hypertension: a single-centre experience from South India.

OBJECTIVE: To study maternal complications and pregnancy outcome in women with pulmonary hypertension, attending a tertiary centre in south India. STUDY DESIGN: Retrospective observational study. SETTING: Tertiary centre in south India. POPULATION: Pregnant women with pulmonary hypertension. METHOD: Data regarding demographics, clinical course, medication received, and echocardiographic diagnosis regarding pulmonary hypertension and antenatal care received were collected from the records. Details of labour and delivery, and postpartum follow up were retrieved. We compared the outcome based on the presence or absence of cyanosis and right ventricular systolic pressure levels. MAIN OUTCOME MEASURES: Maternal mortality, occurrence of complications such as heart failure, fetal growth restriction. RESULTS: There were 81 pregnancies in 73 women with pulmonary hypertension. The majority of them had pulmonary hypertension secondary to congenital heart disease (80.8%); 17.8% had Eisenmenger syndrome. An advanced pulmonary artery hypertension (PAH) medication, sildenafil, was administered in 25 (31.3%) pregnancies. There were four maternal deaths, of which three had Eisenmenger syndrome. Heart failure complicated 6.3% and fetal growth restriction 26.3% of pregnancies. Morbidity was significantly increased in women with pulmonary hypertension associated with a cyanotic cardiac lesion or with right ventricular systolic pressure >70 mmHg. CONCLUSION: Despite advances in care, mortality in pregnant women with pulmonary hypertension is a matter of concern, especially in those with Eisenmenger syndrome. Multidisciplinary team management in tertiary centres and the use of advanced PAH medications even in low- to middle-income countries with limited resources, could lead to a reduction in morbidity and mortality related to pulmonary hypertension. TWEETABLE ABSTRACT: Multidisciplinary care and use of new medication may improve outcomes in pregnant women with pulmonary hypertension.

Eisenmenger Syndrome in Adults: Treatment Pattern and Prognostic Factors in the Advanced Pulmonary Vasodilator Era.

Patients with Eisenmenger syndrome (ES) have a higher mortality rate than patients with simple congenital heart disease (CHD). To determine factors associated with death in the era of advanced pulmonary vasodilator treatment, we analyzed the characteristics of adult ES patients depending on underlying CHD. Simple septal defects and patent ductus arteriosus were classified as simple CHD, and other conditions were classified as complex CHD. Sixty-seven adult ES patients (50.7% women) were reviewed retrospectively. CHD was diagnosed at a median of 10.0 years of age and ES was diagnosed at 18.6 years. Thirteen patients (19.4%) died; the median age was 38.6 years (IQR 32.2-47.8). In a multivariate analysis, patients with SpO2 < 85% had a higher mortality rate than others [hazard ratio (HR) 9.7; 95% confidence interval (CI) 1.002-95.2, p = 0.05]. In simple CHD patients, those with a low platelet count (< 100 × 109/L) or low SpO2 (< 85%) were at a higher risk of death than those without (HR 16.32, 95% CI 1.25-2266.31, p = 0.032; and HR 38.91, 95% CI 3.44-5219.41, p = 0.001, respectively). Advanced pulmonary vasodilators were used more in survivors than in non-survivors (48.1% vs. 15.4%, p = 0.032). Low SpO2 and platelet count were related to mortality in adult ES, especially in those with simple CHD. Therefore, careful attention should be paid to the care of adult ES patients with this tendency; active pulmonary vasodilator treatment should be considered.

Contemporary survival of patients with pulmonary arterial hypertension and congenital systemic to pulmonary shunts.

OBJECTIVE: To compare survival of patients with newly diagnosed pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD) according to various clinical classifications with classifications of anatomical-pathophysiological systemic to pulmonary shunts in a single-center cohort. METHODS: All prevalent cases of PAH-CHD with hemodynamic confirmation by cardiac catheterization in 1995-2015 were retrospectively reviewed. Patients who were younger than three months of age, or with single ventricle following surgery were excluded. Baseline characteristics and clinical outcomes were retrieved from the database. The survival analysis was performed at the end of 2016. Prognostic factors were identified using multivariate analysis. RESULTS: A total of 366 consecutive patients (24.5 ± 17.6 years of age, 40% male) with PAH-CHD were analyzed. Most had simple shunts (85 pre-tricuspid, 105 post-tricuspid, 102 combined shunts). Patients with pre-tricuspid shunts were significantly older at diagnosis in comparison to post-tricuspid, combined, and complex shunts. Clinical classifications identified patients as having Eisenmenger syndrome (ES, 26.8%), prevalent left to right shunt (66.7%), PAH with small defect (3%), or PAH following defect correction (3.5%). At follow-up (median = 5.9 years; 0.1-20.7 years), no statistically significant differences in survival rate were seen among the anatomical-pathophysiological shunts (p = 0.1). Conversely, the clinical classifications revealed that patients with PAH-small defect had inferior survival compared to patients with ES, PAH post-corrective surgery, or PAH with prevalent left to right shunt (p = 0.01). Significant mortality risks were functional class III, age < 10 years, PAH-small defect, elevated right atrial pressure > 15 mmHg, and baseline PVR > 8 WU•m.2. CONCLUSION: Patients with PAH-CHD had a modest long-term survival. Different anatomical-pathophysiological shunts affect the natural presentation, while clinical classifications indicate treatment strategies and survival. Contemporary therapy improves survival in deliberately selected patients.

Platelet count and mean platelet volume predict outcome in adults with Eisenmenger syndrome.

OBJECTIVES: Although a significant proportion of patients with cyanotic congenital heart disease are thrombocytopaenic, its prevalence and clinical significance in adults with Eisenmenger syndrome (ES) is not well studied. Accordingly, we examined the relationship of thrombocytopaenia and mean platelet volume (MPV) to bleeding or thrombotic complications and survival in a contemporary cohort of patients with ES, including patients with Down syndrome. METHODS: Demographics, laboratory and clinical data were analysed from 226 patients with ES under active follow-up over 11 years. RESULTS: Age at baseline was 34.6±11.4 years and 34.1% were men. Mean platelet count and MPV were 152.6±73.3×109/L and 9.6±1.2 fL, respectively. A strong inverse correlation was found between platelet count and haemoglobin concentration and MPV. During the study, there were 39 deaths, and 21 thrombotic and 43 bleeding events. On univariate Cox regression analysis, patients with a platelet count <100×109/L had a twofold increased mortality (HR 2.10, 95% CI 1.10 to 4.01, p=0.024). Platelet count was not associated with an increased risk of thrombosis. However, there was a threefold increased thrombotic risk with MPV >9.5 fL (HR 3.50, 95% CI 1.28 to 9.54, p=0.015). Patients with either severe secondary erythrocytosis (>220g/L) or anaemia (<130g/L) were at higher risk of thrombotic events (HR 3.93, 95% CI 1.60 to 9.67, p=0.003; and HR 4.75, 95% CI 1.03 to 21.84, p=0.045, respectively). CONCLUSIONS: Thrombocytopaenia significantly increased the risk of mortality in ES. Furthermore, raised MPV, severe secondary erythrocytosis and anaemia, but not platelet count, were associated with an increased risk of thrombotic events in our adult cohort.

Past and current cause-specific mortality in Eisenmenger syndrome.

AIMS: Eisenmenger syndrome (ES) is associated with considerable morbidity and mortality. Therapeutic strategies have changed during the 2000s in conjunction with an emphasis on specialist follow-up. The aim of this study was to determine the cause-specific mortality in ES and evaluate any relevant changes between 1977 and 2015. METHODS AND RESULTS: This is a retrospective, descriptive multicentre study. A total of 1546 patients (mean age 38.7 ± 15.4 years; 36% male) from 13 countries were included. Cause-specific mortality was examined before and after July 2006, 'early' and 'late', respectively. Over a median follow-up of 6.1 years (interquartile range 2.1-21.5 years) 558 deaths were recorded; cause-specific mortality was identified in 411 (74%) cases. Leading causes of death were heart failure (34%), infection (26%), sudden cardiac death (10%), thromboembolism (8%), haemorrhage (7%), and peri-procedural (7%). Heart failure deaths increased in the 'late' relative to the 'early' era (P = 0.032), whereas death from thromboembolic events and death in relation to cardiac and non-cardiac procedures decreased (P = 0.014, P = 0.014, P = 0.004, respectively). There was an increase in longevity in the 'late' vs. 'early' era (median survival 52.3 vs. 35.2 years, P < 0.001). CONCLUSION: The study shows that despite changes in therapy, care, and follow-up of ES in tertiary care centres, all-cause mortality including cardiac remains high. Patients from the 'late' era, however, die later and from chronic rather than acute cardiac causes, primarily heart failure, whereas peri-procedural and deaths due to haemoptysis have become less common. Lifelong vigilance in tertiary centres and further research for ES are clearly needed.

Cardiovascular and general health status of adults with Trisomy 21.

BACKGROUND: Patients with Trisomy 21 are now living well into adulthood. Little data exists to assist the cardiologist in the care of these patients. We sought to examine the cardiac and general health status of adults with Trisomy 21 undergoing cardiac evaluation. METHODS & RESULTS: A retrospective review of all affected adults >21years followed at 2 tertiary care institutions was performed. Of 193 patients identified, median age was 31 (range 21.1-60.5) years. Cardiac surgery was performed in childhood in 127 with 30 patients who did not undergo surgery developing Eisenmenger syndrome. The remaining 36 patients did not warrant early surgical intervention. Six patients were lost to follow-up. Significant cardiac residua were present in 117 (62%). Arrhythmias were present in 53 (28%) with 15 having atrial fibrillation (8%). Non-cardiac comorbidities were common and included sleep apnea, pulmonary hypertension, thyroid dysfunction, thromboses and recurrent infections. Hospitalization in adulthood occurred in 58 patients (51%); pneumonia and cardiac related surgeries being the most common reasons for hospitalization. Average age of death (n=23) was 39.8±8.5years. Transition of care to an adult provider was uncommon occurring in 54 (27%) patients. On multivariate analysis, presence of younger age and absence of pulmonary hypertension were the sole predictors of survival for the group as a whole, as well as those patients without Eisenmenger syndrome. CONCLUSIONS: Adults with Trisomy 21 have frequent cardiac and non-cardiac co-morbidities. Cardiologists caring for these patients should be familiar with the adult acquired medical problems these patients encounter.

Outcome of adults with Eisenmenger syndrome treated with drugs specific to pulmonary arterial hypertension: A French multicentre study.

BACKGROUND: The relationship between pulmonary arterial hypertension-specific drug therapy (PAH-SDT) and mortality in Eisenmenger syndrome (ES) is controversial. AIMS: To investigate outcomes in patients with ES, and their relationship with PAH-SDT. METHODS: Retrospective, observational, nationwide, multicentre cohort study. RESULTS: We included 340 patients with ES: genetic syndrome (n=119; 35.3%); pretricuspid defect (n=75; 22.1%). Overall, 276 (81.2%) patients received PAH-SDT: monotherapy (endothelin receptor antagonist [ERA] or phosphodiesterase 5 inhibitor [PDE5I]) 46.7%; dual therapy (ERA+PDE5I) 40.9%; triple therapy (ERA+PDE5I+prostanoid) 9.1%. Median PAH-SDT duration was 5.5 years [3.0-9.1 years]. Events (death, lung or heart-lung transplantation) occurred in 95 (27.9%) patients at a median age of 40.5 years [29.4-47.6]. The cumulative occurrence of events was 16.7% [95% confidence interval 12.8-21.6%] and 46.4% [95% confidence interval 38.2-55.4%] at age 40 and 60 years, respectively. With age at evaluation or time since PAH diagnosis as time scales, cumulative occurrence of events was lower in patients taking one or two PAH-SDTs (P=0.0001 and P=0.004, respectively), with the largest differences in the post-tricuspid defect subgroup (P<0.001 and P<0.02, respectively) versus patients without PAH-SDT. By multivariable Cox analysis, with time since PAH diagnosis as time scale, New York Heart Association/World Health Organization functional class III/IV, lower peripheral arterial oxygen saturation and pretricuspid defect were associated with a higher risk of events (P=0.002, P=0.01 and P=0.04, respectively), and one or two PAH-SDTs with a lower risk of events (P=0.009). CONCLUSIONS: Outcomes are poor in ES, but seem better with PAH-SDT. ES with pretricuspid defects has worse outcomes despite the delayed disease onset.

Éxitus materno tras cesárea en gestante con anomalía de Taussig-Bing y síndrome de Eisenmenger / Maternal Exitus after Cesarean Section in Pregnant Women with Taussig-Bing Anomaly and Eisenmenger Syndrome

La anomalía de Taussig-Bing es una cardiopatía congénita cianosante caracterizada por la dextrotransposición de grandes vasos. Esta produce una doble salida arterial desde el ventrículo derecho, asociado a una comunicación interventricular. Este cuadro puede generar una hipertensión pulmonar secundaria al aumento de las resistencias vasculares y un flujo reverso cardiaco, conocido como síndrome de Eisenmenger. Normalmente, se presenta antes de la pubertad, aunque en ocasiones, puede debutar en la vida adulta, progresando durante dicha etapa. Clínicamente, se caracteriza por rasgos crónicos, como las acropaquias, la disnea, la sensación de cansancio o la cianosis. El diagnóstico de este tipo de cardiopatías se basa en la clínica y en las pruebas de imagen, preferentemente en el estudio ecocardiográfico fetal o durante la edad pediátrica. El tratamiento de elección es la corrección quirúrgica de las malformaciones cardiacas, siendo preferente la rectificación de la salida de la aorta y el cierre de la comunicación interventricular. El pronóstico depende del grado de hipertensión pulmonar, del momento del diagnóstico y de la corrección quirúrgica precoz. A edades tempranas se obtiene un mejor resultado, aunque las tasas de mortalidad alcanzan 50 por ciento en algunos casos, incluso tras una corrección quirúrgica óptima. La gestación no está recomendada en pacientes que padecen dicha patología, la cual se ha contraindicado, según algunos estudios, en ausencia de tratamiento adecuado. Así pues, describimos un caso en el que una gestante con una anomalía Taussig-Bing sufre una atonía uterina y un posterior paro cardiorrespiratoria tras el parto, realizado mediante cesárea electiva, tras la que la paciente falleció(AU)

The Taussig-Bing anomaly is a congenital cyanosis characterized by the dextrotransposition of large vessels. It produces a double arterial exit from the right ventricle, associated with an interventricular communication. This may lead to pulmonary hypertension secondary to increased vascular resistance and a cardiac reverse flow, known as Eisenmenger syndrome. Generally, it occurs before puberty, although occasionally, it can debut in adults, progressing during that stage. It is clinically characterized by chronic features, such as acropachies, dyspnea, tiredness or cyanosis. The diagnosis of this type of heart disease is based on clinical exam and imaging tests, if at all possible in the fetal echocardiographic study or during the pediatric age. The surgical correction of cardiac malformations is the treatment of choice, modifying the aortic exit and closing of ventricular septal defect. The prognosis depends on the degree of pulmonary hypertension, the time of diagnosis, and the early surgical correction. Better outcome is obtained at early ages, although mortality rates reach 50 percent in some cases, even after optimal surgical correction. Pregnancy is not recommended in patients suffering from this disease. Some studies contraindicate pregnancy in absence of proper treatment. Thus, we describe a case of a pregnant woman with a Taussig-Bing anomaly, who suffered uterine atony and a subsequent cardiorespiratory arrest after delivery. Elective cesarean section was performed. This patient died(AU)

Éxitus materno tras cesárea en gestante con anomalía de Taussig-Bing y síndrome de Eisenmenger / Maternal Exitus after Cesarean Section in Pregnant Women with Taussig-Bing Anomaly and Eisenmenger Syndrome

La anomalía de Taussig-Bing es una cardiopatía congénita cianosante caracterizada por la dextrotransposición de grandes vasos. Esta produce una doble salida arterial desde el ventrículo derecho, asociado a una comunicación interventricular. Este cuadro puede generar una hipertensión pulmonar secundaria al aumento de las resistencias vasculares y un flujo reverso cardiaco, conocido como síndrome de Eisenmenger. Normalmente, se presenta antes de la pubertad, aunque en ocasiones, puede debutar en la vida adulta, progresando durante dicha etapa. Clínicamente, se caracteriza por rasgos crónicos, como las acropaquias, la disnea, la sensación de cansancio o la cianosis. El diagnóstico de este tipo de cardiopatías se basa en la clínica y en las pruebas de imagen, preferentemente en el estudio ecocardiográfico fetal o durante la edad pediátrica. El tratamiento de elección es la corrección quirúrgica de las malformaciones cardiacas, siendo preferente la rectificación de la salida de la aorta y el cierre de la comunicación interventricular. El pronóstico depende del grado de hipertensión pulmonar, del momento del diagnóstico y de la corrección quirúrgica precoz. A edades tempranas se obtiene un mejor resultado, aunque las tasas de mortalidad alcanzan 50 % en algunos casos, incluso tras una corrección quirúrgica óptima. La gestación no está recomendada en pacientes que padecen dicha patología, la cual se ha contraindicado, según algunos estudios, en ausencia de tratamiento adecuado. Así pues, describimos un caso en el que una gestante con una anomalía Taussig-Bing sufre una atonía uterina y un posterior paro cardiorrespiratoria tras el parto, realizado mediante cesárea electiva, tras la que la paciente falleció(AU)

The Taussig-Bing anomaly is a congenital cyanosis characterized by the dextrotransposition of large vessels. It produces a double arterial exit from the right ventricle, associated with an interventricular communication. This may lead to pulmonary hypertension secondary to increased vascular resistance and a cardiac reverse flow, known as Eisenmenger syndrome. Generally, it occurs before puberty, although occasionally, it can debut in adults, progressing during that stage. It is clinically characterized by chronic features, such as acropachies, dyspnea, tiredness or cyanosis. The diagnosis of this type of heart disease is based on clinical exam and imaging tests, if at all possible in the fetal echocardiographic study or during the pediatric age. The surgical correction of cardiac malformations is the treatment of choice, modifying the aortic exit and closing of ventricular septal defect. The prognosis depends on the degree of pulmonary hypertension, the time of diagnosis, and the early surgical correction. Better outcome is obtained at early ages, although mortality rates reach 50% in some cases, even after optimal surgical correction. Pregnancy is not recommended in patients suffering from this disease. Some studies contraindicate pregnancy in absence of proper treatment. Thus, we describe a case of a pregnant woman with a Taussig-Bing anomaly, who suffered uterine atony and a subsequent cardiorespiratory arrest after delivery. Elective cesarean section was performed. This patient died(AU)

Predictors of Death in Contemporary Adult Patients With Eisenmenger Syndrome: A Multicenter Study.

BACKGROUND: Eisenmenger syndrome is associated with substantial morbidity and mortality. There is no consensus, however, on mortality risk stratification. We aimed to investigate survival and predictors of death in a large, contemporary cohort of Eisenmenger syndrome patients. METHODS: In a multicenter approach, we identified adults with Eisenmenger syndrome under follow-up between 2000 and 2015. We examined survival and its association with clinical, electrocardiographic, echocardiographic, and laboratory parameters. RESULTS: We studied 1098 patients (median age, 34.4 years; range, 16.1-84.4 years; 65.1% female; 31.9% with Down syndrome). The majority had a posttricuspid defect (n=643, 58.6%), followed by patients with a complex (n=315, 28.7%) and pretricuspid lesion (n=140, 12.7%). Over a median follow-up of 3.1 years (interquartile range, 1.4-5.9), allowing for 4361.6 patient-years observation, 278 patients died and 6 underwent transplantation. Twelve parameters emerged as significant predictors of death on univariable analysis. On multivariable Cox regression analysis, only age (hazard ratio [HR], 1.41/10 years; 95% confidence interval [CI], 1.24-1.59; P<0.001), pretricuspid shunt (HR, 1.56; 95% CI, 1.02-2.39; P=0.041), oxygen saturation at rest (HR, 0.53/10%; 95% CI, 0.43-0.65; P<0.001), presence of sinus rhythm (HR, 0.53; 95% CI, 0.32-0.88; P=0.013), and presence of pericardial effusion (HR, 2.41; 95% CI, 1.59-3.66; P<0.001) remained significant predictors of death. CONCLUSIONS: There is significant premature mortality among contemporary adults with Eisenmenger syndrome. We report, herewith, a multivariable mortality risk stratification model based on 5 simple, noninvasive predictors of death in this population.

Cardiac remodelling amongst adults with various aetiologies of pulmonary arterial hypertension including Eisenmenger syndrome-implications on survival and the role of right ventricular transverse strain.

AIMS: Survival in pulmonary arterial hypertension (PAH) and Eisenmenger syndrome (ES) relates to right ventricular (RV) function. Little is known about differences of ventricular function between ES patients and those suffering from other PAH aetiologies. In this study, we compared global ventricular function assessed by speckle-tracking in adult patients with ES, other PAH aetiologies, or healthy controls; and assessed the relationship between ventricular function and survival. METHODS AND RESULTS: We performed a prospective cohort study recruiting 83 adult PAH patients (43 ES and 40 other PAH aetiologies patients) and 37 controls between March 2011 and June 2015. Patients with complex congenital heart disease were excluded. Fifty-three patients (63.9%) were in NYHA functional class ≥III at baseline and 60 (72.3%) were on advanced therapies. Mean RV peak longitudinal strain was -16.3 ± 7% in ES, lower compared with healthy controls (P < 0.001) but similar to other PAH aetiologies (P = 0.6). Mean RV peak transverse strain was +26.1 ± 17% in ES, lower than in controls (P < 0.001) but higher than in other PAH aetiologies (P < 0.001). No difference was observed between ES and other PAH in LV circumferential and longitudinal strain. Over a median follow-up of 22.6 months (3.3-32.2), 22 (26.5%) patients died all from cardio-pulmonary causes. ES and RV peak transverse strain were independent predictors of survival. RV peak transverse strain ≤22% identified patients with a 14-fold increased risk of death. CONCLUSION: Right ventricular remodelling differs between adults with ES and other PAH aetiologies. ES and increased RV free wall transverse strain are associated with better survival.

Pregnancy outcome in women with Eisenmenger's syndrome: a case series from west China.

BACKGROUND: Eisenmenger's syndrome (ES) consists of pulmonary hypertension with a reversed or bidirectional shunt at the atrioventricular, or aortopulmonary level. The cardiovascular changes that occur during the pregnancy contribute to the high maternal morbidity and mortality in patients with ES. This study is to assess maternal and fetal outcomes in patients with ES. METHODS: This study is a retrospective analysis of 11 pregnancies in women with ES who delivered at a tertiary care center in west China between 2010 and 2014. Cases were divided into group I (maternal survival) and group II (maternal death). Clinical data were noted and analyzed. RESULTS: All ES patients presented with severe pulmonary arterial hypertension (PAH). Four maternal deaths were recorded (maternal mortality of 36%). Only one pregnancy continued to term. Ventricular septal defect diameter in group II was larger than that in group I (2.93 ± 0.76 cm vs. 1.90 ± 0.54 cm, p < 0.05). Arterial oxygen saturation and pre-delivery arterial oxygen tension during oxygen inhalation were significantly lower in group II (p < 0.05). Pulmonary arterial blood pressure (PABP) in both groups were high while ejection fractions (EF) were significantly lower in group II (p < 0.05). The incidence of pre-delivery heart failure in group II was substantially higher than in survivors (100 vs.14.3%, p < 0.05). Fetal complications were exceptionally high: preterm delivery (88%), small for gestational age (83%), fetal mortality (27%) and neonatal mortality (25%). CONCLUSIONS: In west China,the perinatal outcome of pregnant women with ES is poor, especially when complicated with high pulmonary arterial hypertension (PAH). Pregnancy remains strongly contraindicated in ES. Effective contraception is essential, and the option of terminating pregnancy in the first trimester should be presented to pregnant women with ES.

Eisenmenger syndrome and long-term survival in patients with Down syndrome and congenital heart disease.

OBJECTIVE: To characterise patients with trisomy 21 (Down syndrome, DS) based on the data of the German National Register for Congenital Heart Defects, to identify changes in the availability of surgical therapy over time and to analyse the impact of these changes on developing Eisenmenger syndrome (ES) as well as survival. METHODS: Out of 1549 patients with DS with congenital heart disease in the National Register for Congenital Heart Defects, 894 patients (55% female, mean age 17.5 years) had a post-tricuspid shunt lesion (atrioventricular septal defect 69.5%, ventricular septal defect 27.7%, patent arterial duct 2.6%) and were included in the current study. RESULTS: The likelihood of being treated interventionally or surgically before the age of 1 year increased significantly over time. In parallel, the likelihood of developing ES decreased over time (53% birth cohort during 1950s/1960s vs 0.5% birth cohort during 2000-2009, p<0.0001). Overall survival after 1, 10, 20 and 40 years was 96.8%, 94.1%, 92.6% and 75.5%, respectively. Patients with ES had a significantly worse survival compared with those without ES (HR 18.1; 95% CI 7.2 to 45.4; p<0.0001). CONCLUSIONS: The availability of surgical correction was associated with a decrease in the likelihood of developing ES. Patients with DS still have reduced survival prospects compared with the general population, but this effect is largely driven by patients developing ES who still have a very poor prognosis.

Survival and outcomes of patients with unoperated single ventricle.

OBJECTIVE: Patients with unoperated single ventricle (SV) rarely survive into adulthood with good functional status and may develop Eisenmenger's syndrome (ES). We report outcomes of a 30-year cohort of such patients. METHODS: Adult patients with unoperated SV were identified by searching the Mayo Clinic medical record from 1984 to 2014. Clinical data were collected and compared between patients with pulmonary stenosis (PS) and ES. RESULTS: 24 patients were identified (median peak-age 56 (31-77) years (11 ES, 13 PS); 22 had left ventricular morphology. 50-year transplant-free survival was 65% (95% CI 43 to 81). Median age at death was 55 years (31-77 years); 15 deaths (62%) occurred before oral pulmonary vasodilators were commercially available. Two-thirds of the cohort demonstrated preserved New York Heart Association functional class and median EF was 60% (49% to 62%). The majority of patients to survive into the fifth decade exhibited anatomy of double-inlet LV (DILV) with PS. CONCLUSION: Selected patients with unoperated SV with PS and ES can survive with good functional class up to the eighth decade with good medical management. DILV/PS appears to be the ideal phenotype for advanced survival. Our outcomes may be considered when such patients with SV having 'balanced' physiology are evaluated for Fontan palliation. However, additional prospective study will be necessary to verify this assertion.

Impaired Right, Left, or Biventricular Function and Resting Oxygen Saturation Are Associated With Mortality in Eisenmenger Syndrome: A Clinical and Cardiovascular Magnetic Resonance Study.

BACKGROUND: Patients with Eisenmenger syndrome (ES) have better survival, despite similar pulmonary vascular pathology, compared with other patients with pulmonary arterial hypertension. Cardiovascular magnetic resonance (CMR) is useful for risk stratification in idiopathic pulmonary arterial hypertension, whereas it has not been evaluated in ES. We studied CMR together with other noninvasive measurements in ES to evaluate its potential role as a noninvasive risk stratification test. METHODS AND RESULTS: Between 2003 and 2005, 48 patients with ES, all with a post-tricuspid shunt, were enrolled in a prospective, longitudinal, single-center study. All patients underwent a standardized baseline assessment with CMR, blood test, echocardiography, and 6-minute walk test and were followed up for mortality until the end of December 2013. Twelve patients (25%) died during follow-up, mostly from heart failure (50%). Impaired ventricular function (right or left ventricular ejection fraction) was associated with increased risk of mortality (lowest quartile: right ventricular ejection fraction, <40%; hazard ratio, 4.4 [95% confidence interval, 1.4-13.5]; P=0.01 and left ventricular ejection fraction, <50%; hazard ratio, 6.6 [95% confidence interval, 2.1-20.8]; P=0.001). Biventricular impairment (lowest quartile left ventricular ejection fraction, <50% and right ventricular ejection fraction, <40%) conveyed an even higher risk of mortality (hazard ratio, 8.0 [95% confidence interval, 2.5-25.1]; P=0.0004). No other CMR or noninvasive measurement besides resting oxygen saturation (hazard ratio, 0.90 [0.83-0.97]/%; P=0.007) was associated with mortality. CONCLUSIONS: Impaired right, left, or biventricular systolic function derived from baseline CMR and resting oxygen saturation are associated with mortality in adult patients with ES. CMR is a useful noninvasive tool, which may be incorporated in the risk stratification assessment of ES during lifelong follow-up.

Physiological differences between various types of Eisenmenger syndrome and relation to outcome.

BACKGROUND: Eisenmenger syndrome (ES) is the most advanced form of pulmonary arterial hypertension (PAH) related to congenital heart disease. Several studies have suggested that the presence and location of the shunt defines the natural history of these patients by influencing right ventricular adaptation to PAH. We aimed to echocardiographically assess differences in cardiac physiology and outcome between various types of ES. METHODS AND RESULTS: In this longitudinal cohort study, 191 patients with ES and non-complex congenital heart disease were recruited, 36 with pre-tricuspid and 155 with post-tricuspid shunts. Patients with pre-tricuspid shunts were older, had higher BNP concentrations and lower exercise tolerance compared to patients with post-tricuspid shunts. Right ventricular (RV) function was impaired in patients with atrial septal defects, with larger right ventricles, impaired systolic function and adaptation. The left ventricular eccentricity index was significantly higher in pre-tricuspid defects. Within post-tricuspid shunts, patients with atrio-ventricular septal defects had better right ventricular function compared to ventricular septal defects, while in those with a patent ductus arteriosus this was worse. There was a trend towards lower mortality in patients with post versus pre-tricuspid shunts, which was significant for patients above the age of 48 years. CONCLUSION: The presence of a post-tricuspid shunt appears to carry physiological and possibly prognostic benefits in ES compared to patients with pre-tricuspid shunts. This should be borne in mind when management decisions and advanced therapies are considered.