Elisabeth Bédard

Has there been any progress made on pregnancy outcomes among women with pulmonary arterial hypertension

Pregnancy in women with pulmonary arterial hypertension (PAH) is considered to be associated with prohibitive maternal mortality. During the past decade, new advanced therapies for PAH have emerged and progress in high-risk pregnancy management has been made. We examined whether these changes have improved outcomes in parturients with PAH. A systematic review of all cases of parturients with idiopathic pulmonary hypertension (iPAH), congenital heart disease associated with PAH (CHD-PAH), or PAH of other aetiology (oPH) published in the past decade (1997-2007) was performed. Outcome data from this study were then compared with relevant data published between 1978 and 1996. Forty-eight case reports or case series met the inclusion criteria, totalling 73 parturients with PAH. Seventy-two per cent of patients with iPAH were receiving advanced therapies, compared with 52% of CHD-PAH and 47% of oPH. Although a publication bias cannot be excluded, overall maternal mortality was significantly lower compared with previous era (25 vs. 38%, P = 0.047) and was 17% in iPAH, 28% in CHD-PAH, and 33% in oPH. Seventy-eight per cent of deaths occurred within the first month after delivery. Primigravidae and parturients who received general anaesthesia were at higher risk of death (OR 3.70, 95% CI 1.15-12.5, P = 0.03 and OR 4.37, 95% CI 1.28-16.50, P = 0.02, respectively). Maternal mortality in parturients with PAH remains prohibitively high, despite lower death rates than previous decades. Early advice on pregnancy risks, including contraception, remains paramount. Women with PAH who become pregnant warrant a multidisciplinary approach with consideration of advanced therapies.

Circulating Endothelial Progenitor Cells in Patients With Eisenmenger Syndrome and Idiopathic Pulmonary Arterial Hypertension

Background— Impaired endothelial homeostasis underlies the pathophysiology of pulmonary arterial hypertension (PAH). We speculated that PAH patients are deficient in circulating endothelial progenitor cells (EPCs), potentially contributing to endothelial dysfunction and disease progression. Methods and Results— We recruited 41 patients with Eisenmenger syndrome (13 with Down syndrome), 55 with idiopathic PAH, and 47 healthy control subjects. Flow cytometry and in vitro assays were used to quantify EPCs and to assess cell function. The number of circulating CD34+, CD34+/AC133+, CD34+/KDR+, and CD34+/AC133+/KDR+ progenitor cells was low in Eisenmenger patients compared with healthy control subjects, and those with Down syndrome displayed even fewer EPCs. Reductions in EPC numbers correlated with New York Heart Association functional class, 6-minute walk distance, and plasma brain-type natriuretic peptide levels. The capacity of cultured peripheral blood mononuclear cells to form colonies and incorporate into tube-like structures was impaired in Eisenmenger patients. Idiopathic PAH patients had reduced numbers of EPCs, and the number of circulating EPCs correlated with invasive hemodynamic parameters in this cohort. Levels of immune inflammatory markers, cGMP, stable nitric oxide oxidation products, and asymmetric dimethylarginine were abnormal in patients with PAH and related to numbers of EPCs. Within the idiopathic PAH population, treatment with the phosphodiesterase inhibitor sildenafil was associated with a dose-dependent rise in EPC numbers, resulting in levels consistently above those found with other therapies. Conclusions— Circulating EPC numbers are reduced in 2 well-characterized forms of PAH, which also exhibit raised levels of inflammatory mediators. Sildenafil treatment may represent a pharmacological means of increasing circulating EPC numbers long-term.

Burden of Coronary Artery Disease in Adults With Congenital Heart Disease and Its Relation to Congenital and Traditional Heart Risk Factors

As adult patients with congenital heart disease (CHD) grow older, the risk of developing coronary artery disease (CAD) increases. We sought to estimate the prevalence of CAD in adult patients with CHD, the safety of coronary angiography in this setting, and the potential relation of CAD to clinical and hemodynamic parameters. Two hundred fifty adult patients with CHD (mean age 51 +/- 15 years; 53% men) underwent selective coronary angiography in our center for reasons other than suspected CAD. Clinical and hemodynamic data were retrieved retrospectively from medical records and echocardiographic and angiographic databases, respectively. Significant CAD using quantitative coronary angiography was found in 9.2% of adult patients with CHD. No patient with cyanosis or age <40 years had significant CAD. Systolic and diastolic systemic ventricular dimensions were significantly higher in patients with CAD, even after adjustment for age (odds ratio [OR] for 10-mm increase 2.59, 95% confidence interval [CI] 1.29 to 5.21, p = 0.007; OR 2.31, 95% CI 1.24 to 4.31, p = 0.008, respectively). Systemic arterial hypertension and hyperlipidemia were strong predictors of CAD (OR 4.54, 95% CI 1.82 to 12.0, p = 0.001; OR 9.08, 95% CI 3.56 to 24.54, p <0.0001, respectively), whereas no relation to chest pain was found. Only 1 major adverse event was recorded during coronary angiography. In conclusion, the prevalence of significant CAD in a hospital adult CHD cohort was similar to that in the general population. This study supported the performance of selective coronary angiography in patients >40 years referred for cardiac surgery, with low risk of major complications. Traditional cardiovascular risk factors for CAD also applied to adult patients with CHD, in whom primary prevention of CAD was as important as in the general population.

Usefulness of natriuretic peptide levels to predict mortality in adults with congenital heart disease

Neurohormonal activation is prevalent in adults with congenital heart disease, but its relation to outcome remains unknown. B-type natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) were measured prospectively in 49 patients with adult congenital heart disease, who were followed up for a median of 7.9 years (interquartile range 7.7 to 8.2). Cox proportional hazards regression analysis was used to determine the relation of BNP and ANP concentrations to all-cause mortality. The mean age at baseline was 33.9 +/- 11.3 years, and 46.9% of patients were men. Most patients (77.5%) were symptomatic (20.4% had New York Heart Association class III), 10 (20.4%) were cyanotic, and 28 (57.1%) had systemic ventricular dysfunction (moderate or severe in 18.4%). The median concentration of BNP was 52.7 pg/ml (interquartile range 39.1 to 115.4) and of ANP was 47.4 pg/ml (interquartile range 19.7 to 112.8). Of the 49 patients, 11 (22.4%) died during the follow-up period. Both BNP and ANP were strong predictors of mortality (hazard ratio per 100-pg/ml increase 1.80, 95% confidence interval 1.38 to 2.34, p <0.0001; and hazard ratio per 100-pg/ml increase 1.21, 95% confidence interval 1.12 to 1.32, p <0.0001, respectively). A BNP value >78 pg/ml predicted death with a sensitivity of 100% and specificity of 76.3% (area under the curve 0.91, p = 0.0001). An ANP value of >146 pg/ml predicted death with a sensitivity of 72.7% and specificity 94.7% (area under the curve 0.89, p = 0.0001). No patients with a BNP level <78 pg/ml died during the follow-up period. In conclusion, the BNP and ANP levels strongly predicted death in symptomatic ambulatory patients with adult congenital heart disease during mid-term follow-up and could be used as a simple clinical marker for risk stratification in this population.

First-in-man Experience of a Novel Transcatheter Repair System for Treating Severe Tricuspid Regurgitation

BACKGROUND Isolated tricuspid valve surgery is associated with high morbidity and mortality, especially in patients with prior cardiac surgery. The transcatheter Forma Repair System (Edwards Lifesciences, Irvine, California) is designed to provide a surface for native leaflet coaptation to reduce tricuspid regurgitation (TR) by occupying the regurgitant orifice area. OBJECTIVES This study sought to evaluate the feasibility and exploratory efficacy with this transcatheter repair system for the treatment of severe TR. METHODS Seven high-risk patients with severe TR and clinical signs of heart failure were declined for surgery and offered transcatheter treatment with this device. All procedures were performed within a cardiac catheterization laboratory or hybrid operating room under general anesthesia with transesophageal echocardiographic guidance. Vascular access was via the left axillary vein. Baseline characteristics, procedural and in-hospital outcomes, as well as 30-day follow-up were prospectively collected. RESULTS All patients had severe TR and New York Heart Association (NYHA) functional class II to IV (mean age 76 ± 13 years; mean logistic EuroSCORE 25.7 ± 17.4%), and underwent device implantation to improve tricuspid leaflet coaptation, thereby reducing TR. Device implantation was successful without procedural complications in all patients, with significant reductions in TR severity (moderate in 3 patients and mild in 4 patients). Median hospital length of stay was 4 days. At 30-day follow-up, all patients but 1 demonstrated improvements in NYHA functional status (to class II) with pronounced reductions in the presence and severity of peripheral edema. TR severity was assessed as being moderate at 30-day transthoracic echocardiography follow-up in all patients. No complications related to the device or vascular access were observed during follow-up. CONCLUSIONS A transcatheter-based treatment option for severe TR appears safe and feasible with this repair system. Improvements in TR severity were documented in all patients, which were accompanied by improvements in peripheral edema and functional status.

Adult congenital heart disease: a 2008 overview

INTRODUCTION During the past decades, health care of patients born with congenital heart disease (CHD) has improved substantially, leading to a growing population of adult survivors. SOURCE OF DATA Using the recently published and relevant data on adult CHD (ACHD), we reviewed the most common congenital heart defects and discussed important related issues. AREAS OF AGREEMENT Adults with CHD most often require specialized medical or surgical care in a tertiary centre. However, this population also need local follow-up; general practitioners and other specialists therefore have to face the complexity of their disease. AREAS OF CONTROVERSIES: Management of pregnancy, non-cardiac surgery, arrhythmias and endocarditis prophylaxis may be challenging in patients with CHD and should be adapted to their condition. GROWING POINTS The present article summarizes key clinical information on ACHD for the benefit of physicians who are not specialized in this field. Areas timely for developing research Research efforts and education strategies are greatly needed in order to optimize the care of patients with ACHD.

Exercise capacity and impact of exercise training in patients after a Fontan procedure: A review

After a successful Fontan procedure, children and adolescents should improve their exercise capacity. However, several studies have shown that these children have a reduced maximal oxygen consumption compared with healthy children. The lower exercise performance in these patients was mainly explained by a reduced cardiorespiratory functional capacity. However, it has recently been reported that the lower exercise performance may also be related to altered skeletal muscle function. Moreover, exercise training had a beneficial impact on several parameters related to exercise tolerance in these patients. The main studies supporting these observations are reviewed, with a focus on the physiological adaptation and limitation of the exercise performance as well as the benefits of exercise training in patients after a Fontan procedure.

Impact of hypertension and renin-angiotensin system inhibitors in aortic stenosis.

Experimental studies revealed that renin–angiotensin system (RAS) could play a crucial role in the pathophysiology of aortic stenosis (AS). The objectives of this study were to examine (i) the impact of hypertension on AS progression and clinical events and (ii) the effect of angiotensin‐converting enzyme inhibitors (ACEIs) and angiotensin‐receptor blockers (ARBs).

Enhanced Thrombogenesis but Not Platelet Activation Is Associated With Transcatheter Closure of Patent Foramen Ovale in Patients With Cryptogenic Stroke

Background and Purpose— No studies have yet determined whether antiplatelet or anticoagulant therapy is the more appropriate treatment after transcatheter closure of patent foramen ovale (PFO) in patients with cryptogenic stroke. The objective of this study was to prospectively evaluate the presence, degree, and timing of activation of the platelet and coagulation systems after transcatheter closure of PFO in patients with cryptogenic stroke. Methods— Twenty-four consecutive patients (mean age, 44±10 years; 11 men) with previous cryptogenic stroke who had undergone successful transcatheter closure of PFO were included in the study. Prothrombin fragment 1+2 (F1+2) and thrombin–antithrombin III (TAT) were used as markers of coagulation activation, and soluble P-selectin and soluble CD40 ligand were used as markers of platelet activation. Measurements of all hemostatic markers were taken at baseline just before the procedure and at 7, 30, and 90 days after device implantation. Results— F1+2 and TAT levels increased from 0.41±0.16 nmol/L and 2.34±1.81 ng/mL, respectively, at baseline to a maximal value of 0.61±0.16 nmol/L and 4.34±1.83 ng/mL, respectively, at 7 days, gradually returning to baseline levels at 90 days (P<0.001 for both markers). F1+2 and TAT levels at 7 days after PFO closure were higher than those obtained in a group of 25 healthy controls (P<0.001 for both markers). Levels of soluble P-selectin and soluble CD40 ligand did not change at any time after PFO closure. Conclusions— Transcatheter closure of PFO is associated with significant activation of the coagulation system, with no increase in platelet activation markers. These findings raise the question of whether optimal antithrombotic treatment after PFO closure should be short-term anticoagulant rather than antiplatelet therapy.

Structural Abnormalities of the Pulmonary Trunk in Tetralogy of Fallot and Potential Clinical Implications : A Morphological Study

OBJECTIVES The purpose of this study was to determine whether intrinsic histological abnormalities of the pulmonary trunk (PT) are present from birth and interact with palliative surgery and/or repair. BACKGROUND Little is known about PT histology in patients with tetralogy of Fallot (TOF), especially in the era of surgical intervention in childhood. METHODS We studied 39 formalin-fixed necropsy heart specimens with TOF and compared them with 17 normal control heart specimens. Sections of the PT and aorta were studied by light microscopy using various stains; histological findings were graded according to severity. RESULTS Among the TOF group (1 fetus, 11 infants, 14 children, and 13 adults), 11 patients had undergone palliative and 10 patients had undergone reparative surgery at a median age of 8 years (range 2.5 to 18 years). Histological changes of grade 2 or higher were present in 59% (medionecrosis), 36% (fibrosis), 56% (cystlike formation), and 56% (abnormal elastic tissue configuration) of TOF patients. Total histology grading scores were higher in TOF hearts (median 6, range 1 to 9) compared with controls (median 1, range 0 to 6; p < 0.0001). Histological abnormalities were present among infants (median score 3.5, range 1 to 9) and after palliative surgery (median score 5, range 2 to 9) or repair (median score 7.5, range 4 to 9). CONCLUSIONS Marked histological abnormalities in the PT of hearts with TOF exist compared with controls. These changes were present from infancy and among patients who had undergone palliative or reparative surgery, although operations in this cohort were performed late. Our data suggest that structural abnormalities of the PT, similar to these recently shown in the aorta, are intrinsic.