BACKGROUND—The Fontan procedure has improved survival in children with functionally univentricular hearts. With time, however, complications such as reduced exercise capacity are seen more ...frequently. Exercise intolerance is multifactorial, but pulmonary vascular resistance probably plays a crucial role. Elevated pulmonary vascular resistance has been associated with raised levels of endothelin-1, which are common both before and after Fontan operations. Treatment with endothelin-1 receptor antagonists could theoretically improve cardiopulmonary hemodynamics and exercise capacity. The aim of this study was therefore to examine the efficacy and safety of bosentan in Fontan patients.
METHODS AND RESULTS—Seventy-five adolescents and adults were randomized 1:1 to 14 weeks of treatment with bosentan or placebo. Cardiopulmonary exercise test, functional class, blood samples, and quality-of-life questionnaires were evaluated at baseline and at the end of treatment. Sixty-nine patients (92%) completed the study. Peak oxygen consumption increased 2.0 mL·kg·min (from 28.7 to 30.7 mL·kg·min) in the bosentan group compared with 0.6 mL·kg·min (from 28.4 to 29.0 mL·kg·min) in the placebo group (P=0.02). Cardiopulmonary exercise test time increased by 0.48 minute (from 6.79 to 7.27 minutes) versus 0.08 minute (from 6.94 to 7.02 minutes; P=0.04). Nine bosentan-treated patients improved 1 functional class, whereas none improved in the placebo group (P=0.0085). Side effects were mild and occurred equally in both groups. No serious adverse effects were seen, and no patients had liver enzyme levels above the 3-fold upper limit.
CONCLUSIONS—Bosentan improves exercise capacity, exercise time, and functional class in Fontan patients without serious adverse events or hepatotoxicity.
CLINICAL TRIAL REGISTRATION—URLhttp://www.clinicaltrials.gov. Unique identifierNCT01292551.
Abstract Background After the Fontan procedure patients are at risk for reduced quality of life (QoL) and cognitive function. We aimed to assess these important factors in Danish Fontan patients and ...to compare the results with a group of healthy controls. Methods All Fontan patients living in Denmark were identified and invited to participate. QoL was evaluated using the Pediatric Quality of Life Inventory (PedsQL) version 4.0 generic core module in patients < 16 years and the Short Form 36 questionnaire (SF-36) in patients ≥ 16 years. Cognitive function was evaluated in all patients ≥ 6 years using the Quick Test of Cognitive Speed. To evaluate if QoL correlated with exercise capacity, patients performed a symptom-limited bicycle test. Results 158 of 179 eligible patients (88%) consented to participate. Median age was 13.9 years (IQR: 10.2–19.3). PedsQL scores increased with age but were significantly lower among patients than among controls. SF-36 physical scores were significantly lower in patients compared to controls while psychosocial scores were similar. Cognitive speed was significantly reduced in patients at all ages compared to controls. No significant difference in PedsQL-/SF-36 scores or cognitive speed was found between hypoplastic left heart syndrome (HLHS) and non-HLHS Fontan patient. PedsQL-/SF-36 scores in patients ≥ 10 years correlated significantly to cognitive speed but not to peak exercise capacity. Conclusion QoL is reduced in Fontan children compared to their healthy counterparts whereas in patients ≥ 16 years only physical, but not psychosocial QoL is reduced. Cognitive speed was significantly lower in patients at all ages compared to controls.
Fixed pulmonary hypertension (FPH) is considered a contraindication to cardiac transplantation. Ventricular assist device (VAD) therapy through prolonged left ventricular unloading may reverse FPH. ...Our aim was to assess post-transplant outcomes and survival in patients with and without FPH undergoing VAD implantation as bridge to transplant.
Fifty-four patients received an intracorporeal left VAD (LVAD) as a bridge to transplant from 2000 to 2008 at two institutions (Rigshospitalet, Denmark, and the Toronto General Hospital, Canada). Twenty-two (41%) patients had fixed FPH (defined as pulmonary vascular resistance PVR >3 Wood units and resistant to pulmonary vasodilators) prior to VAD implant (FPH group) and were compared with 32 patients without FPH (NoFPH group). Baseline characteristics, pre- and post-transplant pulmonary pressures, incidence of complications and post-transplant survival were analyzed.
Baseline characteristics were similar except that patients in the FPH group were older (46 ± 11 years vs 39 ± 13 years in the NoFPH group, p < 0.05). The mean pre-VAD PVR was 4.3 ± 1.7 Wood units in the FPH group and 1.7 ± 0.5 Wood units in the NoFPH group (p < 0.001). Pulmonary pressures were higher in the FPH group immediately prior to VAD implant, but they were comparable immediately pre-transplant and during the first year post-transplant. The incidence of post-transplant RV failure was not significantly different between groups. Post-transplant survival was similar between groups.
VAD therapy successfully decreases pulmonary hypertension, even in patients with "fixed" FPH, allowing candidacy for heart transplantation. Among bridge-to-transplant candidates, the presence of FPH does not reduce post-transplant survival.
Coarctation of the aorta (CoA), a congenital narrowing of the proximal descending thoracic aorta, is a relatively common form of congenital heart disease. Untreated significant CoA has a major impact ...on morbidity and mortality. In the past 3 decades, transcatheter intervention (TCI) for CoA has evolved as an alternative to surgery.
The authors report on all TCIs for CoA performed from 2000 to 2016 in 4 countries covering 25 million inhabitants, with a mean follow-up duration of 6.9 years.
During the study period, 683 interventions were performed on 542 patients.
The procedural success rate was 88%, with 9% considered partly successful. Complications at the intervention site occurred in 3.5% of interventions and at the access site in 3.5%. There was no in-hospital mortality. During follow-up, TCI for CoA reduced the presence of hypertension significantly from 73% to 34%, but despite this, many patients remained hypertensive and in need of continuous antihypertensive treatment. Moreover, 8% to 9% of patients needed aortic and/or aortic valve surgery during follow-up.
TCI for CoA can be performed with a low risk for complications. Lifetime follow-up after TCI for CoA seems warranted.
Advancing ecological restoration assessments requires a more detailed consideration of species interactions and ecosystem processes. Most restoration projects rely on a few metrics not always ...directly linked with ecological theory. Here, we used Odum's theory of ecosystem development to assess and compare the ecosystem structure and services of created marshes (4–6 years old) with preexisting, reference marshes in a brackish water region of the Mississippi River Delta. We built ecosystem models for created and reference marshes that integrated large datasets of stomach contents, stable isotopes, and taxa abundances. Despite strong resemblance in community structure, created marshes were at an earlier succession stage compared to the reference marshes, having lower biomass (including exploited species), higher biomass turnover and production, less dependence on detritus, lower material cycling, and less energy flowing through specialist pathways. Although preserving preexisting marshes should be a priority, created marshes may still be an important tool for the restoration of coastal areas and their ecosystem services. In addition, our results show that comparisons of species biodiversity alone may fail to capture essential differences in ecosystem processes between habitats, which reinforces the importance of ecosystem modeling approaches to assess restoration projects.
Coastal wetlands are rapidly disappearing worldwide due to a variety of processes, including climate change and flood control. The rate of loss in the Mississippi River Delta is among the highest in ...the world and billions of dollars have been allocated to build and restore coastal wetlands. A key question guiding assessment is whether created coastal salt marshes have similar biodiversity to preexisting, reference marshes. However, the numerous biodiversity metrics used to make these determinations are typically scale dependent and often conflicting. Here, we applied ecological theory to compare the diversity of different assemblages (surface and below‐surface soil microbes, plants, macroinfauna, spiders, and on‐marsh and off‐marsh nekton) between two created marshes (4–6 years old) and four reference marshes. We also quantified the scale‐dependent effects of species abundance distribution, aggregation, and density on richness differences and explored differences in species composition. Total, between‐sample, and within‐sample diversity (γ, β, and α, respectively) were not consistently lower at created marshes. Richness decomposition varied greatly among assemblages and marshes (e.g., soil microbes showed high equitability and α diversity, but plant diversity was restricted to a few dominant species with high aggregation). However, species abundance distribution, aggregation, and density patterns were not directly associated with differences between created and reference marshes. One exception was considerably lower density for macroinfauna at one of the created marshes, which was drier because of being at a higher elevation and having coarser substrate compared with the other marshes. The community compositions of created marshes were more dissimilar than reference marshes for microbe and macroinfauna assemblages. However, differences were small, particularly for microbes. Together, our results suggest generally similar taxonomic diversity and composition between created and reference marshes. This provides support for the creation of marsh habitat as tools for the maintenance and restoration of coastal biodiversity. However, caution is needed when creating marshes because specific building and restoration plans may lead to different colonization patterns.
Background:
Patients with psychiatric illness have increased somatic morbidity and increased mortality. Knowledge of how to integrate the prevention and care of somatic illness into the treatment of ...psychiatric patients is required. The aims of this study were to investigate whether an intervention programme to improve physical health is effective.
Methods:
An extension of the European Network for Promoting the Health of Residents in Psychiatric and Social Care Institutions (HELPS) project further developed as a 12-month controlled cluster-randomized intervention study in the Danish centre. Waist circumference was a proxy of unhealthy body fat in view of the increased risk of cardiovascular diseases and type 2 diabetes.
Results:
Waist circumference was 108 cm for men and 108 cm for women. Controlled for cluster randomization, sex, age, and body fat, the intervention group showed a small, but not significant, reduction in waist circumference, while participants in the control group showed a significant increase in waist circumference.
Conclusions:
The intervention had a positive effect on the physical health of the patients measured by a reduction in the increase of waist circumference.
End-stage heart failure is associated with impaired cardiac output (CO) and organ blood flow. We determined whether CO and peripheral perfusion are maintained during exercise in patients with an ...axial-flow left ventricular assist device (LVAD) and whether an increase in LVAD pump speed with work rate would increase organ blood flow.
Invasively determined CO and leg blood flow and Doppler-determined cerebral perfusion were measured during 2 incremental cycle exercise tests on the same day in 8 patients provided with a HeartMate II LVAD. In random order, patients exercised both with a constant (≈9775 rpm) and with an increasing pump speed (+400 rpm per exercise stage). At 60 W, the elevation in CO was more pronounced with increased pump speed (8.7±0.6 versus 8.1±1.1 L · min(-1); mean±SD; P=0.05), but at maximal exercise increases in CO (from 7.0±0.9 to 13.6±2.5 L · min(-1); P<0.01) and leg blood flow 0.7 (0.5 to 0.8) to 4.4 (3.9 to 4.8) L · min(-1) per leg; median (range); P<0.001 were similar with both pumping modes. Normally, middle cerebral artery mean flow velocity increases from ≈50 to ≈65 cm · s(-1) during exercise, but in LVAD patients with a constant pump speed it was low at rest (39±14 cm · s(-1)) and remained unchanged during exercise, whereas in patients with increasing pump speed, it increased by 5.2±2.8 cm · s(-1) at 60 W (P<0.01).
With maximal exercise, the axial-flow LVAD supports near-normal increments in cardiac output and leg perfusion, but cerebral perfusion is poor. Increased pump speed augments cerebral perfusion during exercise.
Treatment options for patients with Eisenmenger syndrome have until recently been scarce, but new knowledge in the field of pulmonary arterial hypertension has expanded the therapeutic possibilities ...for these patients. Advanced therapy with pulmonary vasodilators has become part of the standard treatment, offering long-term benefits on exercise capacity, clinical symptoms and possibly survival. However, there are currently only few studies to guide the use of advanced therapies in this population and important questions such as indications for initiation or escalation of advanced therapy, as well as valid effect parameters and treatment goals, remain unanswered. This review covers the pharmacology, therapeutic options, risk stratification, and treatment strategy of pulmonary arterial hypertension-specific drugs in patients with Eisenmenger syndrome.
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.
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.
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.
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