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Impact of Pulmonary Hypertension on Survival Following Device Closure of Atrial Septal Defects
Abstract
Pulmonary hypertension (PH), defined as mean pulmonary arterial pressure ≥25 mm Hg, may be a complication of a secundum atrial septal defect (ASD). This study sought to evaluate the impact of PH at time of ASD device closure on patient survival. A prospectively collected database of ASD closures was utilized. Patients were stratified by age above and below the cohort median (48 years). Survival was analyzed by preprocedural PH status, age cohort, and echocardiographic resolution of PH at 3 months postdevice closure. PH was present in 48 of 228 patients (21.1%) and was more common in the older cohort (31.3% vs 10.6%, p <0.01). ASD size was unrelated to the presence of PH (p = 0.33). Older patients had more medical co-morbidities including diabetes (p = 0.02), hyperlipidemia (p <0.01), and systemic hypertension (p <0.01) compared with younger patients. PH did not impact survival in patients ≤48 years, but PH was associated with fivefold increased risk of death in patients >48 years (p < 0.01). Patients with preprocedural PH and RVSP ≥40 mm Hg at 3-month follow-up continued to have an increased risk of mortality (p <0.01), whereas those with resolution of PH had similar survival to those without PH at time of closure. In conclusion, PH is common in adults with unrepaired ASDs and appears unrelated to defect size. PH in older adults and its persistence closure are strong predictors of a worsened clinical outcome. These patients may benefit from additional risk assessment and advanced medical therapies to mitigate this risk.
... Pulmonary hypertension (PH) represents an important risk factor associated with reduced functional capacity and increased mortality in patients with atrial septal defect (ASD) (1)(2)(3)(4)(5)(6). Moreover, persistence of PH after ASD closure is strongly associated with increased mortality (4,7,8). On the other hand, patients with normalization of PH after ASD closure have similar outcome as patients without PH (7). ...
... Moreover, persistence of PH after ASD closure is strongly associated with increased mortality (4,7,8). On the other hand, patients with normalization of PH after ASD closure have similar outcome as patients without PH (7). The decision of whether to close ASD in patients with PH presents a complex clinical dilemma (9,10). ...
... The guidelines give limits for safe defect closure for pulmonary vascular resistance (PVR) < 3 Wood Units (WU) or 4 WU × m 2 and contraindication of defect closure for PVR more than 5 WU or 8 WU × m 2 (2,11,12). However, the guidelines do not specify the probability of PH normalization after defect closure, an important factor for survival (4,7,8). Moreover, many studies (including guidelines) deal only with pulmonary arterial hypertension (PAH) in congenital shunt lesions (2,3,13,14), although it is just one of four hemodynamic types of PH in adults with ASD (9,15). ...
Pulmonary hypertension (PH) is an established risk factor in patients with atrial septal defect (ASD), and its persistence after ASD closure is associated with increased mortality. Therefore, predictors for PH normalization after defect closure are needed. Multiple hemodynamic types of PH exist, but little is known about their prevalence and prognostic value for PH normalization after ASD closure. We carried out a retrospective study on 97 patients (76% female, median age at ASD closure 58 years) with four types of PH determined predominantly by right heart catheterization: hyperkinetic, pulmonary arterial hypertension, isolated post-capillary, and combined pre- and post-capillary. We investigated the frequency of the PH types and their prognostic significance for PH normalization after ASD closure. Frequency of PH types before ASD closure in our study was: hyperkinetic 55%, pulmonary arterial hypertension 10%, isolated post-capillary PH 24%, and combined PH 11%. Hyperkinetic PH type was positively associated with PH normalization after ASD closure (78% patients normalized), remaining a significant independent predictor when adjusted for age at closure, sex, heart failure, and NYHA. Hyperkinetic PH patients also had significantly better survival prognosis versus patients with other PH types ( p = 0.04). Combined PH was negatively associated with PH normalization, with no patients normalizing. Pulmonary arterial hypertension and isolated post-capillary PH had intermediate rates of normalization (60 and 52%, respectively). In summary, all four hemodynamic types of PH are found in adult patients with ASD, and they can be used to stratify patients by their likelihood of PH normalization and survival after ASD closure.
... One particularly important group with unclear closure benefit comprises patients with pulmonary hypertension (PH). ASD closure appears safe in young patients without PH or even with PH meeting the criteria for defect closure (2)(3)(4)(5)(6). However, the presence of PH in older patients is associated with increased mortality following ASD closure compared to patients without PH (3,4). ...
... ASD closure appears safe in young patients without PH or even with PH meeting the criteria for defect closure (2)(3)(4)(5)(6). However, the presence of PH in older patients is associated with increased mortality following ASD closure compared to patients without PH (3,4). It is not known whether the poor prognosis of the PH patients results from the ASD closure itself, or if their outcome would have been similar or even worse if the ASD closure was not carried out. ...
... The decision concerning ASD closure is particularly difficult in elderly patients with PH given the increased mortality risk in this group after ASD closure compared to young patients or patients without PH (3,4,11,12). The previous studies were missing a control group of patients without ASD closure, and thus could not distinguish whether the worsened survival is due to ASD closure itself, or PH and older age (3). ...
Background
Atrial septal defect (ASD) is the most common congenital heart disease (CHD) in adults and pulmonary hypertension (PH) is an established risk factor. A decision whether to perform ASD closure, especially in elderly patients with PH, is a complex dilemma. The aim of our study was to compare long-term survival in patients with closed and open ASD.
Methods
A retrospective cohort study was performed on 427 patients with ASD (median age at diagnosis 38 years, IQR 18–56) out of which 186 patients (44%) manifested PH. ASD closure in patients with PH was only considered in patients without Eisenmenger syndrome with pulmonary vascular resistance < 5 WU. Median follow-up duration was 18 years (IQR 9–31 years). Kaplan-Meier and Cox proportional hazards survival analyses were performed to evaluate 12 potential predictors of survival.
Results
Defect closure was associated with improved long-term survival in ASD patients both with ( P < 0.001) and without PH ( P = 0.01) and this association was present also in patients over 40 years. The 20-year survival since diagnosis was significantly higher in patients with PH and closed ASD compared to those with PH and open ASD (65% vs. 41%). ASD closure was a significant independent predictor of long-term survival ( P = 0.003) after accounting for age at diagnosis, PH, NYHA class, Eisenmenger syndrome, and mitral regurgitation. Significant negative independent predictors of survival were older age at diagnosis ( P < 0.001), Eisenmenger syndrome ( P < 0.001), and PH ( P = 0.03).
Conclusion
ASD closure appears to be associated with improved long-term survival independently of age, PH, and other clinical variables.
... Consistent with past studies, we observed that PH patients had a higher burden of baseline comorbidities than patients without PH. 10,18,30,34,35 Given the scarcity of literature, existing studies are heterogenous in reporting long-term outcomes in this population. Although adverse events were rare, higher rates were observed in patients with PH 20 . ...
... Previous estimates of all-cause mortality in patients undergoing ASD closure ranged from 7-8% during average follow-up from 1.6 to 7.4 years. 30,32,33 Under the new cutoff, patients with PH had a significanlty higher hazard of all-cause mortality in unadjusted but not in adjusted analyses. With a cutoff of mPAP ≥25 mm Hg, the HR of all-cause mortality was 3.0 in unadjusted and 1.5 in adjusted analysis. ...
... The only prior study of comparative survival reported that patients >48 years old with preprocedural PH 25 undergoing percutaneous closure of ASD had an increased risk of mortality compared with those without (Table S6); however, it reported only the unadjusted comparison and used the mPAP ≥25 mm Hg cutoff. 30 We defined the MACCE composite end point as development of a HF, stroke, myocardial infarction, or cardiovascular mortality and found that patients with PH 20 had a significantly higher risk of MACCE. HF was the most frequent adverse event, followed by MACCE defined as heart failure, stroke, myocardial infarction, or CV mortality. ...
Background:
Pulmonary hypertension (PH), recently redefined as mean pulmonary arterial pressure >20 mm Hg (PH20), may be observed in patients with atrial septal defects (ASD). We aimed to determine the effect of preprocedural PH20 status on outcomes among patients undergoing ASD closure.
Methods:
Study population was selected from a retrospective registry of adult patients who underwent percutaneous ASD closure from 1998 to 2016 from a single center and had right heart catheterizations during the procedure. The clinical registry was linked to administrative databases to capture short- and long-term outcomes.
Results:
We included a total of 632 ASD closure patients of whom 359 (56.8%) had PH20. The mean follow-up length was 7.6±4.6 years. Patients with PH20 were older (mean age 56.5 versus 43.1 years, P<0.001) and a higher prevalence of comorbidities including hypertension (54.3% versus 21.6%, P<0.001) and diabetes (18.1% versus 5.9%, P<0.001) than those without PH. In a Cox proportional hazards model after covariate adjustment, patients with PH had a significantly higher risk of developing major adverse cardiac and cerebrovascular events (heart failure, stroke, myocardial infarction, or cardiovascular mortality), with hazards ratio 2.45 (95% CI, 1.4-4.4). When applying the prior, mean pulmonary arterial pressure ≥25 mm Hg (PH25) cutoff, a significantly higher hazard of developing major adverse cardiac and cerebrovascular events was observed in PH versus non-PH patients.
Conclusions:
ASD patients with PH undergoing closure suffer from more comorbidities and worse long-term major adverse cardiac and cerebrovascular events outcomes, compared with patients without PH. The use of the new PH20 definition potentially dilutes the effect of this serious condition on outcomes in this population.
... This study also stated that survival in this group was similar to survival of idiopathic PAH and was significantly worse compared to patients with PAH-small shunts and Eisenmenger syndrome [8]. Similar results were found by Ranard, et al. (2019), who reported that patients with persistence of PAH at the three-month follow-up had increased risk of mortality compared with patients that had resolution of PAH [27]. ...
... This study also stated that survival in this group was similar to survival of idiopathic PAH and was significantly worse compared to patients with PAH-small shunts and Eisenmenger syndrome [8]. Similar results were found by Ranard, et al. (2019), who reported that patients with persistence of PAH at the three-month follow-up had increased risk of mortality compared with patients that had resolution of PAH [27]. ...
... Anatomical-pathophysiological classification of congenital left to right shunts associated with pulmonary arterial hypertension (adapted from Simmoneau, et al.)[27]. ...
Background:
In low-to-middle-income countries, repair of the left-to-right shunts congenital heart disease (CHD) are often done with existing pulmonary arterial hypertension (PAH). Long-term outcomes data of this condition in either low-to-middle or high-income countries are limited. We conducted a study to evaluate the outcomes of children with PAH related to left-to-right shunt CHD who underwent surgical or transcatheter repair.
Methods:
All cases of PAH related to left-to-right shunt CHD repairs from 2015-2018 were retrospectively reviewed with additional new patients who underwent repair within our study period (2019-2020). Cases with complex congenital heart disease and incomplete hemodynamic echocardiography or catheterization measurements were excluded. Kaplan-Meier curves, log-rank test, Cox regression with Firth's correction and restricted mean survival time were used for survival analysis.
Results:
Of the 118 patients, 103 patients were enrolled and 15 patients were excluded due to complex congenital heart disease and missing hemodynamic measurements prior to repair. Overall, median age at intervention was 44 months, mPAP mean was 43.17 ± 16.05 mmHg and Pulmonary Vascular Resistance index (PVRi) mean was 2.84 ± 2.09 (WU.m2). Nine patients died after repair. The survival rate for patients with PAH-CHD at 1 day, 30 days and 1400 days (4 years) was 96.1%, 92.1%, and 91.0% respectively. Patients with persisting PAH after correction had -476.1 days (95% confidence interval [CI]: -714.4, -237,8) shorter survival over 4 years of follow up compared to patients with reversed PAH. PVRi was found to be the influencing covariate of the difference of restricted mean survival time between these groups.
Conclusion:
In low-to-middle income settings, with accurate PAH reversibility assessment prior to intervention, repair of left-to-right shunt CHD with existing PAH in children has a favourable outcome. Inferior survival is found in patients with persistence of PAH. PVRi at baseline predicts between-group survival difference.
... According to Simonneau et al. [10] , PH in ASD secundum is related to the size of the inter-atrial defect, gender, and age. However, according to Ranard et al. [11] , the size of the ASD defect ...
... The results of the Spearman correlation test between the inter-atrial septal defect diameter variable and mPAP pressure showed that there was no relationship between the two variables. This is in accordance with the cohort study conducted by Ranard et al. [11] in America it was found that the size of the ASD defect was not associated with PAH, but PAH occurred independently due to other risk factors such as underlying genetic factors. Meanwhile, according to Jain and Dalvi [18] , with increasing age, the shunt volume through the inter-atrial septal defect may increase due to increased pressure when filling the left heart due to hypertension or ischemic heart disease with or without other risk factors. ...
Atrial Septal Defect (ASD) is one of the three most common types of congenital heart disease in the world. Pulmonary arterial hypertension (PAH) is a complication that can be found in patients with secundum type of ASD. There is no research that shows the relationship between patient’s age and defect size with increased pulmonary artery pressure in secundum type of ASD patients in Indonesia, so further research needs to be done. Material and Methods: This study is a retrospective study using an observational analytical research design with cross sectionalapproach. The data from this study were taken from the medical records of ASD patients at the Cardiology and Vascular Department of Dr. Soetomo Public Hospital Surabaya. Results: Sex distribution of patients with secundum ASD was dominated by female patients with a total of 53 people (81.5%), the age distribution of patients was dominated by patients in the age group of 20-24 years as many as 18 people (27.7%). The most common comorbidities in adult secundum ASD patients were hypertension (3.08%) and minor CAD (3.08%). The mean diameter of the secundum ASD defect was 28.03±9.57 mm, and the data for the smallest defect diameter was 4 mm and the largest was 48 mm. Complications of increased PA pressure were dominated by 20 patients with mild PH (30.8%) and the mean mPAP pressure was 39.87±19.03. There were no patients with Eisenmenger syndrome.Conclusion: There was no correlation between patient age and inter-atrial septal diameter with mPAP pressure.
... The degree of pulmonary hypertension (PH) and the effectiveness of fenestrated devices are very debated issues: Ranard et al. [43] observed that PH did not impact survival in patients ≤48 years, but PH was associated with fivefold increased risk of death in patients >48 years (p < 0.01). Patients with preprocedural PH and right ventricle systolic pressure ≥ 40 mmHg at 3-month follow-up continued to have an increased risk of mortality (p < 0.01), whereas those with resolution of PH had similar survival to those without PH at time of closure. ...
Transcatheter device-based closure is considered the first line therapy for congenital secundum atrial septal defect (ASD). The last 20 years literature data have been reviewed to offer an updated reappraisal of current evidences. Anatomical and functional details, appreciated at both pre-procedural and intraprocedural steps, remain of paramount importance for planning ASD transcatheter –based closure procedure. Routes for interventions should include femoral, and eventually the jugular and hepatic vein approaches. Intraprocedural transoesophageal echocardiography (TTE) or intracardiac echocardiography (ICE) is used at least in most complex cases to have the exact definition of the anatomy of the defects. The clinical outcomes are excellent also compared to surgical series with few complications even compare to surgical series. Transcatheter ASD closure represents the first line therapy in secundum ASD. Future developments of device's material and imaging tools are expected to improve safety and long-term efficacy, even in most complex cases.
... 7,8) Despite the limited beneficial impacts on hemodynamics-related quality of life, disease progression, and survival, the currently available pharmaceutical therapies do not cure PAH, and the median survival rate remains less than 3 years from diagnosis, highlighting the urgent need for extensive researches to reveal the molecular mechanisms underlying PAH. 7,8) The pathogenesis of PAH is highly complex, and both environmental and genetic pathogenic factors can impair pulmonary vascular structure and function, thus leading to PAH. 9) The well-established environmental risk factors encompass congenital heart disease (CHD), [10][11][12][13] valvular heart disease, 14,15) virus infection, 16,17) connective tissue disease, [18][19][20] chronic thromboembolism, [21][22][23][24] chronic obstructive pulmonary disease, 25) pulmonary tumor thrombotic microangiopathy, 26,27) intake of chemical drugs or toxins, [28][29][30][31] and long-term exposure to hypoxia. [32][33][34][35] However, emerging evidence has demonstrated that genetic defects play a pivotal role in the pathogenesis of idiopathic PAH, especially for familial PAH, and deleterious mutations in multiple genes, including BMPR2 encoding a receptor of the transforming growth factor-β superfamily, TBX4 encoding a transcription factor, and KCNK3 as well as ABCC8 encoding potassium channels, have been found to cause PAH. ...
Pulmonary arterial hypertension (PAH) refers to a rare, progressive disorder that is characterized by occlusive pulmonary vascular remodeling, resulting in increased pulmonary arterial pressure, right-sided heart failure, and eventual death. Emerging evidence from genetic investigations of pediatric-onset PAH highlights the strong genetic basis underpinning PAH, and deleterious variants in multiple genes have been found to cause PAH. Nevertheless, PAH is of substantial genetic heterogeneity, and the genetic defects underlying PAH in the overwhelming majority of cases remain elusive. In this investigation, a consanguineous family suffering from PAH transmitted as an autosomal-dominant trait was identified. Through whole-exome sequencing and bioinformatic analyses as well as Sanger sequencing analyses of the PAH family, a novel heterozygous SOX17 mutation, NM_022454.4: c.379C>T; p. (Gln127*), was found to co-segregate with the disease in the family, with complete penetrance. The nonsense mutation was neither observed in 612 unrelated healthy volunteers nor retrieved in the population genetic databases encompassing the Genome Aggregation Database, the Exome Aggregation Consortium database, and the Single Nucleotide Polymorphism database. Biological analyses using a dual-luciferase reporter assay system revealed that the Gln127*-mutant SOX17 protein lost the ability to transcriptionally activate its target gene NOTCH1. Moreover, the Gln127*-mutant SOX17 protein exhibited no inhibitory effect on the function of CTNNB1-encode β-catenin, which is a key player in vascular morphogenesis. This research firstly links SOX17 loss-of-function mutation to familial PAH, which provides novel insight into the molecular pathogenesis of PAH, suggesting potential implications for genetic and prognostic risk evaluation as well as personalized prophylaxis of the family members affected with PAH.
... The duration of PAH is clearly a risk factor with older patients more likely to have more severe PAH and poorer prognosis at defect closure. 27,28 One study of 709 ASD patients found that younger patients can have significant PAH 2 and case studies have shown an association between severe PAH and ASD associated with a BMPR2 gene mutation. This patient failed to respond to targeted PAH therapy and lung transplant 29 . ...
Object
Due to substantial progress of medications to treat pulmonary arterial hypertension (PAH), clinicians are now reconsidering interventional procedures for congenital heart disease (CHD) that were previously considered to be contraindicated or high-risk. This study provides a retrospective evaluation of our institutional approach to treat PAH, proceed to CHD defect closure, and then continue PAH treatment, termed “treat-repair-treat”.
Method
We retrospectively reviewed 14 patients with atrial septal defects (ASD) (mean age of 27.9±7.4 years) with significant PAH who underwent defect closure in our hospital between 2010 and 2018. All patients received targeted PAH medications before defect closure.
Results
Pulmonary vascular resistance (PVR) and mean pulmonary artery pressure (mPAP) decreased after targeted therapy (PVR: 5.7±1.8 VS 8.7±2.9 Wood Units, P=0.003; mPAP: 52.2±7.2 VS 57.1±7.4 mmHg, p=0.2). Eventually, all patients underwent successful defect closure without adverse events. The average follow-up duration was 21.1 months. Twelve patients had post-procedure visits with improved symptoms. Five patients underwent post-procedure right heart catheterization (RHC) which confirmed normal pulmonary artery pressure (mPAP≦25mmHg). Two patients discontinued targeted medical therapy against medical advice and both had worsened exercise capacity at their most recent follow up. Repeat RHC confirmed that these 2 patients had persistent, severe PAH.
Conclusion
Our single center results support an effective “treat-repair-repair” strategy for patients with ASD and PAH. Continued targeted PAH treatment and close follow-up remain important after ASD closure. Larger, multi-center studies are needed to confirm our findings.
Aims:
In this nationwide cohort of atrial septal defect (ASD) patients, the largest to date, we report the longest follow-up time with and without closure in childhood and adulthood compared with a general population cohort.
Methods and results:
Using population-based registries, we included Danish individuals born before 1994 who received an ASD diagnosis between 1959 and 2013. All diagnoses were subsequently validated (n = 2277). Using the Kaplan-Meier estimates and Cox proportional hazards regression adjusted for sex, birth year, and a modified Charlson Comorbidity Index, we compared the mortality of ASD patients with that of a birth year and sex matched general population cohort. The median follow-up from ASD diagnosis was 18.1 years (range 1-53 years). Patients with ASD had a higher mortality [adjusted hazard ratio (HR): 1.7; 95% confidence interval (CI): 1.5-1.9] compared with the general population cohort. The adjusted HR 30 days after closure was 1.4 (95% CI: 1.2-1.7), and it was 2.4 (95% CI: 2.0-2.9) for patients without closure.
Conclusion:
Overall, ASD patients had a higher long-term mortality than a general population cohort matched on birth year and gender. Our data indicate a lower relative mortality of those ASD patients undergoing closure than the ASD patients not undergoing closure.
Patients with an atrial septal defect (ASD) and severe pulmonary arterial hypertension (PAH) are considered
ineligible for defect closure surgery because of the risk of right ventricular decompensation and death after
the operation. We report the case of a patient with large ASD and severe PAH who was able to undergo
defect closure surgery successfully following long-term use of combined oral sildenafil and beraprost.
Objective:
To identify echocardiographic factors that correlate with pulmonary hypertension (PH) in adults with ostium secundum atrial septal defect (ASD).
Methods:
Between November 2009 and November 2013, 92 adults with ASD were studied. All had clinical history and transthoracic echocardiogram.
Results:
Thirty-nine percent of patients had severe PH defined as systolic pulmonary artery pressure (sPAP) of 70 mm Hg or more. The size of ASD (31.84±8.21 mm) and a right-sided tricuspid inflow E-wave to tissue Doppler e'-wave ratio >6.2 correlated with severe PH with AUC of 0.704 (CI 95%=0.59 to 0.818, P<.001) and 0.65 (CI 95%=0.531 to 0.773, P<.014), respectively. Multivariate logistic regression showed that sPAP >70 mm Hg was the variable that most precisely correlated with right ventricular (RV) dysfunction as evidenced by TAPSE <17 mm and RV fractional shortening area (RVFSA) <35%. Left ventricular (LV) diastolic function was also significantly reduced in the group with severe PH with mitral inflow E/A ratio of 0.73±0.23 vs 1.13±0.42 in the group without severe PH (sPAP <70 mm Hg, (P=.001). The pulmonary (Qp) to systemic (Qs) cardiac output ratio (3.09±1.12) and right-sided tissue Doppler S <9.5 cm/s most accurately predicted a Tei index >0.55.
Conclusions:
Larger size of ASD using the QP/QS ratio and increased right-sided tricuspid E/e' ratio correlated with severe PH with a sPAP of 70 mm Hg or more. Patients with severe PH had more severe RV dysfunction as evaluated by TAPSE and RVFSA in comparison to those with PH <70 mm Hg. LV diastolic function was also reduced in the severe PH group.
Aim: It is not well known if advancing age influences normal rest or exercise pulmonary artery pressures. The purpose of the study was to evaluate the association of increasing age with measurements of pulmonary artery systolic pressure at rest and with exercise.
Subjects and methods: A total of 467 adults without cardiopulmonary disease and normal exercise capacity (age range: 18–85 years) underwent symptom-limited treadmill exercise testing with Doppler measurement of rest and exercise pulmonary artery systolic pressure.
Results: There was a progressive increase in rest and exercise pulmonary artery pressures with increasing age. Pulmonary artery systolic pressures at rest and with exercise were 25 ± 5 mmHg and 33 ± 9 mmHg, respectively, in those
Background: Atrial septal defect (ASD) represents a common congenital heart malformation, cause of right ventricle (RV)
volume overload, pulmonary hypertension, atrial arrhythmias, and paradoxical emboli. Percutaneous closure represents the
treatment of choice for ASD. However, it is still difficult to associate symptoms to the success of ASD treatment. Objective: To
investigate any possible correlation between transthoracic echocardiography (TTE) findings and patients’ symptoms after ASD
treatment. Materials and Methods: Thirty patients (mean age 49 ± 17 years; 10 younger ≤40 years and 20 > 40 years) underwent
percutaneous closure of ASD type ostium secundum. Every patient underwent clinical examination, electrocardiogram (ECG) and
TTE before procedure and at 1, 6, and 12 months after procedure and a multichoice questionnaire to collect patients’ symptoms
and complain severity. Statistical analysis: Continuous variables were summarized by means and standard deviation. Estimates
of occurrence of events were expressed as percentages. Comparison between mean follow-ups was achieved using paired
t-test sample. Results: At end of follow-up, TTE showed a decrease of RV dimensions (34.4 vs 37.5 mm preclosure; P = 0.01),
pulmonary artery systolic pressure (PAPs 28.4 vs 39.5 mmHg; P = 0.00003), atrial dimensions (51 vs 56 mm; P = 0.085), and of
right myocardial performance index (MPI; 0.39 vs 0.42; P = 0.05). PAPs was significantly reduced in group more than 40-yearsold
(P = 0.00004), while the reduction was not significant in the less or equal than 40 years of age (P = 0.08) group because the
baseline value was significantly lower. Many patients after procedure complained headache, insomnia, palpitations, fatigue, and
dyspnea; but no cardiac morphological abnormalities related to symptoms were found. Conclusions: Our data showed a great
improvement in symptoms and positive cardiac remodeling after closure of ASD, more effective in elderly patients compared to
younger patients. The symptoms are not correlated with the principal disease or procedure.
The presence of severe pulmonary arterial hypertension (PAH) in patients with atrial septal defect (ASD) is still thought to preclude shunt closure, although there are several reports of good clinical outcomes after vasodilator therapy. We report the case of a young woman with ASD and severe PAH who was able to successfully undergo percutaneous shunt closure following 1 year use of the oral endothelin receptor antagonist, bosentan.
To evaluate the effect of age on the clinical benefit of atrial septal defect (ASD) closure in adults.
Functional status, the presence of arrhythmias, right ventricular (RV) remodelling, and pulmonary artery pressure (PAP) were studied in 236 consecutive patients undergoing transcatheter ASD closure [164 females, mean age of 49 ± 18 years, 78 younger than 40 years (Group A), 84 between 40 and 60 years (Group B) and 74 older than 60 years (Group C)]. Defect size [median 22 mm (inter-quartile range, 19, 26 mm)] and shunt ratio [Qp:Qs 2.2 (1.7, 2.9)] did not differ among age groups. Older patients had, however, more advanced symptoms and both, PAP (r = 0.65, P < 0.0001) and RV size (r = 0.28, P < 0.0001), were significantly related to age. Post-interventionally, RV size decreased from 41 ± 7, 43 ± 7, and 45 ± 6 mm to 32 ± 5, 34 ± 5, and 37 ± 5 mm for Groups A, B, and C, respectively (P < 0.0001), and PAP decreased from 31 ± 7, 37 ± 10, and 53 ± 17 mmHg to 26 ± 5, 30 ± 6, and 43 ± 14 mmHg (P < 0.0001), respectively. Absolute changes in RV size (P = 0.80) and PAP (P = 0.24) did not significantly differ among groups. Symptoms were present in 13, 49, and 83% of the patients before and in 3, 11, and 34% after intervention in Groups A, B, and C. Functional status was related to PAP.
At any age, ASD closure is followed by symptomatic improvement and regression of PAP and RV size. However, the best outcome is achieved in patients with less functional impairment and less elevated PAP. Considering the continuous increase in symptoms, RV remodelling, and PAP with age, ASD closure must be recommended irrespective of symptoms early after diagnosis even in adults of advanced age.
Atrial septal defect (ASD) is one of the most common congenital heart defects. Patients may reach adulthood before being diagnosed and sometimes develop pulmonary hypertension (PH). According to the latest Euro Heart Survey on Congenital Heart Disease, 24.77% of ASD patients develop PH. The reasons for this evolution in only some patients are still unknown.
To assess the prevalence of PH in patients with ostium secundum ASD (osASD) in our district and to determine whether the echocardiographic morphology of the defect can be an indicator of evolution to PH.
The study included 181 consecutive patients, mean age 43.1+/-18.4 years, 65.2% women, with a diagnosis of osASD, referred for transthoracic and transesophageal evaluation in our center from January 2000 to September 2008. We assessed right atrial (RA) and ventricular (RV) dimensions, measured the rims and size of the ASD and determined pulmonary artery systolic pressure (PASP) (RV/RA gradient plus a value corresponding to the degree of inferior vena cava collapse). The type of shunt at the atrial level was assessed with intravenous injection of agitated saline. Statistical analysis was performed using SPSS 15.0.
Seventy-seven patients (42.5%) had moderate to severe enlargement of the right heart chambers and 48 (26.5%) had pulmonary hypertension, defined as PASP of over 40 mmHg (equivalent to mean pulmonary artery pressure of 25-30 mmHg). Patients with PH were older (52.8+/-16.9 vs. 39.0+/-17.6 years; p<0.001) and had larger defects (19.7+/-9.6 mm vs. 13.1+/-7.1 mm; p<0.001). The proportion of women was similar in both groups (64.6% in patients with PH vs. 68.75% in those without; p=NS). Most patients with PH had ASDs with more complex shapes on echocardiography. However, some patients with simpler and smaller defects, such as central ASD with a diameter of <5 mm, also developed PH. The prevalence of PH in patients with closed ASDs was much lower: 20.3% vs. 43.75%; p<0.002. Conclusions: According to these data, development of PH in patients with ASD is frequent and seems to be related to the diameter of the defect. However, patients with smaller and simpler defects may also develop PH. This seems to occur at older ages and not to be gender-dependent. Early ASD closure appears to prevent this.
Advances in the management of congenital heart disease (CHD) in children have resulted in growing numbers of adults with CHD. Pulmonary arterial hypertension related to CHD (PAH-CHD) is a common complication, affecting up to 10% of patients; and can arise even after successful and complete defect repair, with severe and potentially fatal consequences. Careful work-up in these patients is essential, particularly hemodynamic assessment, and can help define the most appropriate therapeutic approach. Management can be challenging, but the therapeutic armamentarium is continually expanding and now includes surgical, transcatheter and medical options. Timely correction of defects along with early treatment with advanced medical therapies appears to improve quality of life and possible even improve survival. Interestingly most studies of PAH-CHD have focused on its most severely afflicted patients, those with Eisenmenger Syndrome, making it less certain how to manage PAH-CHD of milder degrees. This review summarizes our current understanding of PAH-CHD and emphasizes the need for close follow-up in specialized centers of care where close collaboration is common practice.
Background/objectives:
Pulmonary arterial hypertension is an important complication in hemodynamically relevant atrial septal defects (ASD) and negatively affects outcome. This retrospective study aimed at (1) estimating the prevalence of pulmonary hypertension (PH) in patients with secundum ASD and (2) identifying predictors of PH development or persistence after ASD closure.
Methods:
Consecutive patients with an isolated secundum ASD from the Belgian Registry on Adult Congenital Heart Disease were studied. Demographic, clinical, echocardiographic and invasive hemodynamic measurements were analyzed. PH was defined upon the echocardiographic PH probability (tricuspid regurgitation velocity≥2.9 m/s).
Results:
PH prevalence in the entire ASD population (295 patients, 68.8% females, mean age 46±21 years) was 15.9% compared to 13.3% in patients after ASD closure. PH after ASD closure was significantly related to mortality (p=0.001), atrial arrhythmia (p<0.001) and right heart failure (p=0.019). Age at repair was the most important predictor for PH (HR 1.11). In the highest tertile of age at repair (>55 years), PH prevalence was the highest (34%) and mean pulmonary artery pressure (mPAP) at catheterization before was related to PH after closure (HR 1.09). Twenty patients in the PH group had mPAP<25 mmHg before closure.
Conclusions:
PH in closed secundum ASD patients is not uncommon. Its prevalence was the highest when the defect was repaired above 55 years of age. Clinical outcome was worse. PH may even develop despite normal mPAP before closure. The present findings raise the question whether the cutoff value for mPAP before closure should be age-adjusted.
The aim of this study was to assess the impact of the diagnosis of pulmonary hypertension (PH) on mortality, morbidity, and health services utilization (HSU) in an adult congenital heart disease (CHD) population.
Although PH is a well-recognized complication of CHD, population-based studies of its significance on the survival and functional capacity of patients are uncommon.
A retrospective longitudinal cohort study was conducted in an adult CHD population with 23 years of follow-up, from 1983 to 2005. The prevalence of PH was measured in 2005. Mortality, morbidity, and HSU outcomes were compared between patients with and without diagnoses of PH using multivariate Cox (mortality and morbidity) and Poisson (HSU) regression models within a subcohort matched for age and CHD lesion type.
Of 38,430 adults alive with CHD in 2005, 2,212 (5.8%) had diagnoses of PH (median age 67 years, 59% women). The diagnosis of PH increased the all-cause mortality rate of adults with CHD more than 2-fold compared with patients without PH (hazard ratio [HR]: 2.69; 95% confidence interval [CI]: 2.41 to 2.99). Morbid complications including heart failure and arrhythmia occurred with a 3-fold higher risk compared with patients without PH (HR: 3.01; 95% CI: 2.80 to 3.22). The utilization of inpatient and outpatient services was increased, especially cardiac catheterization, excluding the index diagnostic study (rate ratio: 5.04; 95% CI: 4.27 to 5.93) and coronary and intensive care hospitalizations (rate ratio: 5.03; 95% CI: 4.86 to 5.20).
A diagnosis of PH in adults with CHD is associated with a more than 2-fold higher risk for all-cause mortality and 3-fold higher rates of HSU, reflecting high morbidity.
Data on closure of atrial septal defects (ASD) in elderly patients with a fenestrated Amplatzer septal occluder (ASO) device is limited.
A hemodynamically significant ASD was closed with a fenestrated ASO in 3 patients with ages >62 years. Prior to implant a 4-mm fenestration was created by balloon dilatation without additional suture fixation just adjacent to the stent part of the device. Indications for fenestration were restrictive left ventricular physiology and/or pulmonary hypertension. Heparin had been administered during and for 48 hours after the procedure. Two patients were maintained on phenprocoumon because of chronic atrial fibrillation, the remaining patient on aspirin and clopidogrel for 3 months after implant. Transesophageal echocardiography (TEE) and hemodynamic evaluation were performed 4-18 months after ASD closure.
A trace or small fenestration through the ASO with left-to-right shunt was detected by TEE in all 3 patients without any hemodynamic significance. No thrombus formation was observed. Pulmonary hypertension improved in the affected patient. Pulmonary arterial wedge pressure and cardiac index improved in the second patient with improvement in heart failure symptoms and of quality of life in both. The third patient, after initial improvement for 6 months, developed significant comorbidities and clinical deterioration at 18 months follow-up.
The modified fenestration of the ASO decreased significantly in size at follow-up. Applying this technique to selected patients judged to be at risk for ASD closure avoids acute decompensation and allows gradual diminuition of right ventricular volume overload during mid-term follow-up.
Pulmonary arterial hypertension (PAH) may develop in patients with atrial septal defects (ASD); however, little is known about associated risk factors and its evolution after transcatheter ASD closure.
We conducted a cohort study on 215 adults with attempted transcatheter ASD closure from 1999 to 2006. Patients were classified according to baseline systolic pulmonary artery pressures as having no (I, <40 mm Hg), mild (II, 40 to 49 mm Hg), moderate (III, 50 to 59 mm Hg), or severe (IV, >or=60 mm Hg) PAH. Independent predictors of moderate or severe PAH were older age (odds ratio [OR], 1.10 per year; P<0.0001), larger ASD (OR, 1.13 per millimeter; P=0.0052), female sex (OR, 3.9; P=0.0313), and at least moderate tricuspid regurgitation (OR, 3.6; P=0.0043). At 15 (interquartile range, 8 to 43) months post-ASD closure, patients with higher baseline pressures were more likely to experience a >or=5-mm Hg decrease (33.7%, 73.9%, 79.2%, and 100.0% in groups I to IV, P<0.0001), with a larger magnitude of reduction (0, 8, 17, and 22 mm Hg; P<0.0001). However, normalization of pressures (<40 mm Hg) occurred less frequently in patients with more advanced PAH (90.2%, 71.7%, 66.7%, and 23.5%, P<0.0001). Among patients with moderate or severe PAH, independent predictors of normalization were lower baseline pressures (OR, 0.91 per mm Hg; P=0.0418) and no more than mild tricuspid regurgitation (OR, 0.14; P=0.0420).
In adults with ASDs, severity of PAH is modulated by age, sex, defect size, and degree of tricuspid regurgitation. Patients with moderate or severe PAH may benefit from substantial reductions in pulmonary artery pressures after transcatheter ASD closure, although the PAH values remain elevated in a sizeable proportion.
In contrast to the wealth of data on isolated systolic hypertension involving the systemic circulation in the elderly, much less is known about age-related change in pulmonary artery systolic pressure (PASP) and its prognostic impact in the general population. We sought to define the relationship between PASP and age, to evaluate which factors influence PASP, and to determine whether PASP is independently predictive of mortality in the community.
A random sample of the Olmsted County, Minn, general population (n=2042) underwent echocardiography and spirometry and was followed up for a median of 9 years. PASP was measured from the tricuspid regurgitation velocity. Left ventricular diastolic pressure was estimated with Doppler echocardiography (E/e' ratio), and arterial stiffening was assessed from the brachial artery pulse pressure. Among 1413 subjects (69%) with measurable PASP (age, 63+/-11 years; 43% male), median PASP was 26 mm Hg (25th to 75th percentile, 24 to 30 mm Hg) and increased with age (r=0.31, P<0.001). Independent predictors of PASP were age, pulse pressure, and mitral E/e' (all P< or =0.003). Increasing PASP was associated with higher mortality (hazard ratio, 2.73 per 10 mm Hg; P<0.001). In subjects without cardiopulmonary disease (any heart failure, coronary artery disease, hypertension, diabetes mellitus, or chronic obstructive lung disease), the age-adjusted hazard ratio was 2.74 per 10 mm Hg (P=0.016).
We provide the first population-based evidence of age-related increase in pulmonary artery pressure, its association with increasing left heart diastolic pressures and systemic vascular stiffening, and its negative impact on survival. Pulmonary artery pressure may serve as a novel cardiovascular risk factor and potential therapeutic target.
Background:
Atrial septal defects have been surgically correctable for more than 30 years. The long-term survival rates among patients treated in the early era of cardiac surgery are poorly documented, but such data are of critical importance to the future medical care, employability, and insurability of these patients.
Methods:
To determine the natural history of surgically corrected atrial septal defects, we studied all 123 patients who underwent repair of an isolated defect (ostium secundum or sinus venosus) at the Mayo Clinic between 1956 and 1960, 27 to 32 years after the procedure. The follow-up status of all patients was determined by written questionnaires and telephone interviews. Hospital records and death certificates were obtained if interim hospitalization or death had occurred.
Results:
The overall 30-year actuarial survival rate among survivors of the perioperative period was 74 percent, as compared with 85 percent among controls matched for age and sex. The perioperative mortality was 3.3 percent (four deaths). Actuarial 27-year survival rates among patients in the younger two quartiles according to age at operation (less than or equal to 11 years and 12 to 24 years) were no different from rates among controls--97 percent and 93 percent, respectively. In the two older quartiles (25 to 41 years and greater than 41 years), 27-year survival rates were significantly less (P less than 0.001)--84 percent and 40 percent, respectively--than in controls (91 and 59 percent). Independent predictors of long-term survival according to multivariate analysis were age at operation (P less than 0.0001) and systolic pressure in the main pulmonary artery before operation (P less than 0.0027). When repair was performed in older patients, late cardiac failure, stroke, and atrial fibrillation were significantly more frequent.
Conclusions:
Among patients with surgically repaired atrial septal defects, those operated on before the age of 25 have an excellent prognosis, but older patients require careful, regular supervision.
A series of 128 consecutive cases of atrial septal defect in adult patients was analyzed from the standpoint of the course and prognosis. The ages of the patients ranged from 18 to 67 years and the ratio of men to women was 1 to 2. Age distribution when compared with life expectancy tables indicated reduced life expectancy. Clinical analysis revealed that three quarters of the patients were symptomatic, but symptoms were mild to moderate and usually nonprogressive. Hemodynamic analysis revealed significant pulmonary hypertension in 22% of the series, of which 15% had high pulmonary vascular resistance, and significant arterial hypoxemia in 14%. The most serious risk factor in atrial septal defect is severe pulmonary hypertension. This complication, which develops in about 14% of patients with atrial septal defect when they are between 20 and 40 years of age, may be rapidly progressive, leading to shunt reversal, disability, and death. Once established, pulmonary hypertension may progress even when the defect is surgically closed. Heart failure occurs usually in older individuals and is associated mostly with chronic atrial arrhythmias rather than pulmonary hypertension.
Between 1955 and 1977, 66 patients ages 60 years or older underwent operative closure of secundum atrial septal defect. Of these, 56 (85%) were catheterized preoperatively. The 56 patients were divided into three groups to assess the effects of pulmonary hypertension on operative mortality, symptoms and longevity. The 17 group 1 patients had peak systolic pulmonary artery pressures (PAPs) of less than 40 mm Hg; the 21 group 2 patients had PAPs of 40-60 mm Hg; and the 18 group 3 patients had PAPs of more than 60 mm Hg. Among the three groups, there was no significant difference in Qp/Qs, right or left atrial pressures, right or left ventricular end-diastolic pressures and Qs, although pulmonary vascular resistance was significantly higher (p less than 0.01) in group 3 than in group 1. Four patients died, yielding an operative mortality of 6%. All four patients had undergone additional operative procedures. Operative mortality was unrelated to preoperative symptom class, PAP or pulmonary vascular resistance. Forty-seven patients were followed up for 2-20 years (mean 6.6 years), and of these, 41 (87%) improved by at least one functional class. Symptomatic benefit occurred in all groups, regardless of preoperative PAP, pulmonary vascular resistance or functional class. Actuarial survival curves showed that longevity at 5 and 10 years postoperatively was significantly increased (p less than 0.01) for patient with atrial septal defect treated surgically compared with that predicted for age-matched patients treated medically.
Out of 709 consecutive patients with isolated secundum atrial septal defect, the pulmonary artery systolic pressure was greater than 50 mm Hg in 118 patients (17%). Pulmonary hypertension was present in 13% of patients under 10 years and in 14% aged 11 to 20 years. The Eisenmenger reaction was present in 9% of the 709 patients. The frequency of the Eisenmenger reaction was high in young patients and was not significantly different in patients in the first and second decades as compared to older patients. None of our patients with pulmonary hypertension resided at high altitude. The high frequency of pulmonary hypertension in our young patients cannot be satisfactorily explained. Autopsy studies suggest that in some, pulmonary hypertension is due to the persistence of the fetal pulmonary vascular pattern.
The surgical closure of an atrial septal defect is frequently recommended for patients over 40 years of age. However, the prognosis for such patients with unrepaired defects is largely unknown, and the outcome for patients operated on after the fourth decade of life has not yet been compared with that for medically treated patients in a controlled follow-up study.
In a retrospective study, we examined the clinical course of 179 consecutive patients with isolated atrial septal defects diagnosed after the age of 40. The 84 patients (47 percent) who underwent surgical repair were compared with the 95 patients (53 percent) who were treated medically. The mean (+/-SD) follow-up period was 8.9 +/- 5.2 years (range, 1 to 26).
Multivariate analysis revealed that surgical closure of the defect significantly reduced mortality from all causes (relative risk, 0.31; 95 percent confidence interval, 0.11 to 0.85). The adjusted 10-year survival rate of surgically treated patients was 95 percent, as compared with 84 percent for the medically treated patients. In addition, surgical treatment prevented functional deterioration, as measured by the New York Heart Association class (relative risk, 0.21; 95 percent confidence interval, 0.08 to 0.55). However, the incidence of new atrial arrhythmias or of cerebrovascular insults in the two groups was not significantly different.
The surgical repair of an atrial septal defect in patients over 40 years of age, as compared with medical therapy, increases long-term survival and limits the deterioration of function due to heart failure. However, surgically treated patients should be followed closely for the onset of atrial arrhythmias so as to reduce the risk of thromboembolic complications.
This study sought to compare the safety, efficacy and clinical utility of the Amplatzer septal occluder (ASO) for closure of secundum atrial septal defect (ASD) with surgical closure.
The clinical utility of a device such as the ASO can only be judged against the results of contemporaneous surgery.
A multicenter, nonrandomized concurrent study was performed in 29 pediatric cardiology centers from March 1998 to March 2000. The patients were assigned to either the device or surgical closure group according to the patients' option. Baseline physical exams and echocardiography were performed preprocedure and at follow-up (6 and 12 months for device group, 12 months for surgical group).
A total of 442 patients were in the group undergoing device closure, whereas 154 patients were in the surgical group. The median age was 9.8 years for the device group and 4.1 years for the surgical group (p < 0.001). In the device group, 395 (89.4%) patients had a single ASD; in the surgical group, 124 (80.5%) (p = 0.008) had a single ASD. The size of the primary ASD was 13.3 +/- 5.4 mm for the device group and 14.2 +/- 6.3 mm for the surgery group (p = 0.099). The procedural attempt success rate was 95.7% for the device group and 100% for the surgical group (p = 0.006).
The early, primary and secondary efficacy success rates were 94.8%, 98.5% and 91.6%, respectively, for the device group, and 96.1%, 100% and 89.0% for the surgical group (all p > 0.05). The complication rate was 7.2% for the device group and 24.0% for the surgical group (p < 0.001). The mean length of hospital stay was 1.0 +/- 0.3 day for the device group and 3.4 +/- 1.2 days for the surgical group (p < 0.001). Mortality was 0% for both groups. The early, primary and secondary efficacy success rates for surgical versus. device closure of ASD were not statistically different; however, the complication rate was lower and the length of hospital stay was shorter for device closure than for surgical repair. Appropriate patient selection is an important factor for successful device closure. Transcatheter closure of secundum ASD using the ASO is a safe and effective alternative to surgical repair.
Pulmonary arterial hypertension (PAH) has devastating consequences in the rheumatic diseases; however, the prevalence in lupus is not well delineated. We searched the University of Toronto lupus database to ascertain the first echocardiogram ordered at their physician's discretion between 1995 and 2002. We reviewed the echocardiogram reports for right ventricular systolic pressure (RVSP), valvular disease, and atrial and ventricular function. The PAH was defined as RVSP > or = 40 mmHg. Patients were divided into three groups: RVSP > or = 40 mmHg, RVSP = 30-39 mmHg and RVSP < 30 mmHg. We analysed potential associations between presence of PAH and lupus including disease activity, organ involvement and anticardiolipin antibodies, both at the time of and any time prior to echocardiography. In total, 129 patients underwent echocardiography. Nine patients' echocardiograms were not obtainable, and three patients were excluded from analysis, as their visit was more than six months from the date of echocardiography. Sixteen patients (14%) had RVSP > or = 40 mmHg, 43 (37%) patients had RVSP of 30-39, and 60 (51%) patients had RVSP < 30 mmHg. There was no statistical difference in disease activity, organ involvement or serology among all three groups. In conclusion, the prevalence of PAH (RVSP > or = 40 mmHg) on first echocardiogram ordered at physician discretion in our cohort was 14%. An RVSP of 30-39 mmHg was found in 37% of patients. Although abnormal, the clinical significance of this finding is unknown. Disease activity, organ involvement and anticardiolipin antibodies were not associated with PAH. Further research is needed to identify the mechanism, response to immunosuppression and impact on quality of life in these patients.
Primary pulmonary hypertension (PPH) is defined clinically by sustained elevation of pulmonary arterial pressure without a demonstrable cause, and is a progressive, often-fatal disease. PPH can be associated with ingestion of appetite suppressants, human immunodeficiency virus infection and certain autoimmune diseases. Familial PPH is known to account for 6% of all cases. Mutations in the gene encoding the bone morphogenetic protein (BMP) type II receptor have been identified in 72% of affected families and 26% of apparently sporadic cases. BMPs are members of the transforming growth factor b superfamily and affect intracellular signalling via Smads and mitogen-activated protein kinases. Evidence supports a 'two-hit' hypothesis in which PPH is triggered by accumulation of genetic and environmental insults in a susceptible individual. Elucidation of the precise molecular and cellular mechanisms underlying PPH will provide a powerful basis for the development of novel therapeutic strategies in the treatment of this devastating condition.
Most of the data about the prevalence of pulmonary arterial hypertension (PAH) are from tertiary centers that are biased toward seeing more severe cases; therefore, the true prevalence of PAH among patients with connective tissue disease is unknown. We sought to determine the point prevalence of undiagnosed PAH in community-based rheumatology practices.
The study design was a multicenter, prospective and retrospective survey and analysis of clinical cases in 50 community rheumatology practices. We evaluated a total of 909 patients with either scleroderma (systemic sclerosis [SSc]) or mixed connective tissue disease (MCTD). If a subject had not been diagnosed as having PAH, then a new Doppler echocardiogram was obtained to measure cardiac parameters, including estimated right ventricular systolic pressure (ERVSP), and a full review of medical records was done.
Of 909 screened patients, 791 were evaluable and completed the study; 669 had not previously been studied for PAH. Of these 669 patients, 89 (13.3%) were found by Doppler echocardiography to have an ERVSP of > or = 40 mm Hg. Of these 89 patients, 82 (92.1%) had SSc and 7 (7.9%) had MCTD. The total prevalence of PAH in the survey was 26.7% (211 of 791 patients, including 122 with known PAH and 89 newly diagnosed as having PAH). Doppler echocardiographic data showed 20 of 89 patients (22.5%) with ERVSP of > or = 50 mm Hg, 20 of 89 patients (22.5%) with increased RV dimension, and 25 of 89 patients (28.1%) with right atrial enlargement. Patients with ERVSP > or = 40 mm Hg had decreased exercise tolerance compared with those with ERVSP <40 mm Hg (27% compared with 9.5%, respectively, were severely symptomatic).
A significant number of patients with SSc or MCTD (13.3%) followed up in a community rheumatology practice setting have undiagnosed elevated ERVSP consistent with PAH.
The presence of irreversible pulmonary hypertension in patients with atrial septal defect (ASD) is thought to preclude shunt closure. We report the case of a woman with plexiform pulmonary arteriopathy secondary to an ostium secundum ASD who was able to successfully undergo percutaneous shunt closure following therapy with chronic intravenous prostacyclin (Flolan). One year after closure, the patient was weaned off Flolan over a period of 7 months following the institution of oral Bosentan therapy. Our case illustrates how aggressive vasodilator therapy with prostaglandins may be capable of reducing pulmonary artery pressure and permitting shunt closure in a patient once considered to have "inoperable" pulmonary arteriopathy.
Right chamber dilatation and right-to-left volumetric unbalance are well-known cardiac consequences of atrial septal defect (ASD) shunt, accounting for most of its long-term complications. Thus, cardiac volumetric unloading is a major aim of ASD closure. Different from surgery, transcatheter option might be considered as an "unbiased" tool to evaluate the cardiac geometric remodeling following ASD closure.
Extent and time-course of cardiac geometric changes were assessed by echocardiography 24 h, 1 and 6 months after percutaneous closure of large ASD (mean diameter 17+/-6 mm, QP/QS 2.2+/-0.9) in 42 asymptomatic patients (age 22+/-18 years).
Transcatheter closure was accomplished using the Amplatzer Septal Occluder device (mean 23+/-7 mm, median 24 mm), achieving a complete occlusion in all patients at the 6-month follow-up control. After ASD closure, right atrial (RA) volume reduced from 45+/-24 to 28+/-12 ml (-37.8%, p<0.001), while left atrial (LA) volume did not significantly change. Inlet and infundibulum right ventricular (RV) end-diastolic diameters reduced by 23+/-2% and 23+/-3%, respectively (p<0.001 for both measurements), although with a different time-course of changes. Finally, transverse left ventricular (LV) end-diastolic diameter increased from 39+/-7 to 44+/-5 mm (+11.4%, p<0.01). These geometric changes resulted in an RV/LV diameter ratio decrease by 34+/-3% (p<0.001). Nearly 90% of cardiac remodeling ensued within 1 month from shunt disappearance (50% within 24 h).
Percutaneous ASD closure results in early and striking cardiac geometric changes that almost completely revert the right-to-left volumetric unbalance. Most of this geometric remodeling ensues within a few weeks from ASD closure.
Surgical closure of atrial septal defect (ASD) provides excellent results. Given the increasing popularity of percutaneous techniques, a comparison between the 2 methods is needed.
Between December 1988 and June 2003, we performed 1284 procedures in 1268 consecutive patients with isolated secundum ASD. Five hundred and thirty-three patients underwent surgical repair of ostium secundum ASD (group A). Seven hundred and fifty-one consecutive patients underwent percutaneous ASD closure (group B). The following outcomes were studied: mortality, morbidity, hospital stay, and efficacy.
There were no postoperative deaths. The overall rate of complications was higher in group A than in group B: 44% (95% CI 39.8%-48.2%) versus 6.9 % (95% CI 5%-8.7%) (P < .0001). Major complications were also more frequent in group A: 16% (95% CI 13%-19%) versus 3.6% (95% CI 2.2%-5.0%) (P = .002). Multiple logistic regression analysis showed that surgery was independently strongly related to the occurrence of total complication (odds ratio [OR] 8.13, 95% CI 5.75-12.20) and of major complications (OR 4.03, 95% CI 2.38-7.35). The occurrence of minor complications was independently related to surgery (OR 7.33, 95% CI 4.75-11.02), childhood (OR 1.52, 95% CI 1.01-2.34), and presence of systemic hypertension (OR 1.35, 95% CI 1.01-4.41). Hospital stay was shorter in group B (3.2 +/- 0.9 vs 8.0 +/- 2.8 days, P < .0001).
Percutaneous ASD closure provides, in experienced hands and in highly specialized centers, excellent results with a lower complication rate and requires a shorter stay in hospital.
Eisenmenger syndrome is characterized by the development of pulmonary arterial hypertension with consequent intracardiac right-to-left shunt and hypoxemia in patients with preexisting congenital heart disease. Because Eisenmenger syndrome is associated with increased endothelin expression, patients may benefit from endothelin receptor antagonism. Theoretically, interventions that have some effect on the systemic vascular bed could worsen the shunt and increase hypoxemia.
The Bosentan Randomized Trial of Endothelin Antagonist Therapy-5 (BREATHE-5) was a 16-week, multicenter, randomized, double-blind, placebo-controlled study evaluating the effect of bosentan, a dual endothelin receptor antagonist, on systemic pulse oximetry (primary safety end point) and pulmonary vascular resistance (primary efficacy end point) in patients with World Health Organization functional class III Eisenmenger syndrome. Hemodynamics were assessed by right- and left-heart catheterization. Secondary end points included exercise capacity assessed by 6-minute walk distance, additional hemodynamic parameters, functional capacity, and safety. Fifty-four patients were randomized 2:1 to bosentan (n=37) or placebo (n=17) for 16 weeks. The placebo-corrected effect on systemic pulse oximetry was 1.0% (95% confidence interval, -0.7 to 2.8), demonstrating that bosentan did not worsen oxygen saturation. Compared with placebo, bosentan reduced pulmonary vascular resistance index (-472.0 dyne.s.cm(-5); P=0.0383). The mean pulmonary arterial pressure decreased (-5.5 mm Hg; P=0.0363), and the exercise capacity increased (53.1 m; P=0.0079). Four patients discontinued as a result of adverse events, 2 (5%) in the bosentan group and 2 (12%) in the placebo group.
In this first placebo-controlled trial in patients with Eisenmenger syndrome, bosentan was well tolerated and improved exercise capacity and hemodynamics without compromising peripheral oxygen saturation.
There is a lack of evidence regarding treatment options for adults with an atrial septal defect (ASD) who present with an open defect or with sequelae after closure of the defect. The aim of this study was to describe the clinical characteristics and treatment of a large cohort of adult patients born with an ASD type II.
Data on the clinical characteristics of 882 ASD II patients (mean follow-up of 4.2 years) included in the Euro Heart Survey on adult congenital heart disease were analysed. At baseline, the defects of 377 patients (mean age 39.2 (16.1) years; 65% females) had been closed, leaving 505 patients (mean age 41.1 (16.4) years; 68% females) with an open ASD. Hemodynamic abnormalities were more prevalent among patients with an open compared to those with a closed defect at baseline: pulmonary arterial hypertension 35% versus 13%; right ventricular (RV) dysfunction 31% versus 8%; and severe RV volume overload 18% versus 1% (all P-values<0.001). These prevalences increased with age, but hemodynamic parameters remained stable during follow-up in nearly all patients with a small defect. Also functional limitations were more common in those with open defects at baseline compared to those with closed defects (54% versus 25%). There was no difference in the prevalence of arrhythmia's. The best independent predictors of functional limitations appeared to be PAH (odds ratio 25.2 (5.8-109.6); P<0.001)) and RV volume overload (odds ratio 2.3 (1.5-3.4; P<0.001)) in a multivariable model. During follow-up, 9 patients died and in 294 patients the defect was closed, in 180 patients surgically, and in 114 patients by device. Among the latter group there were relatively more females (78% vs 66%; P=0.035). In the surgically closed group defects were more "severe". There were substantial differences according to country in the relative frequency of device closure versus surgical closure, as well as the size and hemodynamic severity of the defects closed.
The data from this study provide a cross-section of the kind of adult patients with an ASD that are seen at outpatient clinics for adult congenital heart disease throughout Europe. Taken together, non-operated patients fared significantly worse in all aspects of hemodynamics studied than the patients whose defects had been closed. In moderate or large defects, when not-operated, clinical parameters tend to worsen with time, and closure of such a defect-the sooner the better-seems always to be the preferred treatment option. In the majority of small defects, operation is not necessarily indicated.
Atrial septal defect (ASD) occlusion in adult patients with advanced age and left or right heart diastolic or systolic heart failure and in patients with pulmonary arterial hypertension bears a considerable risk of deterioration of heart failure. Therefore, we conducted this feasibility trial in 15 ASD patients with pulmonary hypertension and/or right heart failure using a fenestrated Amplatzer septal occluder (AGA Medical Corporation, Golden Valley, MN), allowing an overflow of blood in both directions in case of univentricular diastolic or systolic heart failure. In all patients, the device could be implanted without complications. All symptomatic patients showed an improvement in the New York Heart Association (NYHA) class, and no right or left heart decompensation occurred. On echocardiography, right ventricular end diastolic dimension (RVEDD) and pulmonary artery pressure (PAP) decreased significantly, whereas left ventricular end diastolic dimension (LVEDD) increased. Our series of 15 patients with fenestrated ASD occlusion shows that high-risk ASD occlusion can safely be accomplished with excellent clinical results and without complications by a fenestrated occluder.
Age-associated increases in pulmonary artery systolic pressure in the general population.
- Lam CSP
- Borlaug BA
- Kane GC
- Enders FT
- Rodeheffer RJ
- Redfield MM
Percutaneous versus surgical closure of secundum atrial septal defect.
- Butera G
- Carminati M
- Chessa M
- Youssef R
- Drago M
- Giamberti A
- Pomè G
- Bossone E
- Frigiola A