Repeated blood transfusions: Identification of a novel culprit of early graft failure in children.

BACKGROUND: The attrition of right ventricle to pulmonary artery (RV-PA) grafts has been attributed in part to the body's immunologic response. We hypothesized that antibodies developed through blood transfusion, directed against the grafts, may result in accelerated degeneration and the need for re-intervention. METHODS: This is a population-based study of the province of Quebec. We included children born between January 1, 1987 to December 31, 2006 who were diagnosed with a cono-truncal anomaly and had an RV-PA graft. The patients were followed for transfusion exposure and RV-PA graft re-intervention. Time to re-intervention in those exposed versus non-exposed was analyzed using Cox regression. Analysis was done in two time periods, before and after the calendar year 2000, given the change in blood preparation in the province of Quebec. RESULTS: There were 413 patients who met the inclusion criteria of a cono-truncal disorder. Of the whole study population, 69% received a blood transfusion. Cox regression analysis showed that among patients who had the initial graft performed (n=181) before year 2000, having 2 or more blood transfusion was associated with an nearly tripled risk of a re-intervention comparing to no blood transfusion (hazard ratio of 2.88; 95% confidence interval 1.05-7.91). In patients who had the initial graft performed after year 2000 (n=232), the associated risk increase was 7-fold (hazard ratio of 7.01; 95% confidence interval 3.06-16.02). Kaplan-Meier analyses confirmed the significant difference in the re-intervention free survival probabilities between those who received 2 or more blood product transfusion and those who did not as well: prior to year 2000 (67.9% vs. 88.0% at 5years, p=0.0201) as well as after year 2000 (39.7% vs. 82.8% at 5years, p<0.0001). CONCLUSION: In this population-based analysis, repeated blood product transfusion was associated with a significant increased risk of a need for RV-PA graft re-intervention. This data strongly suggest that repeated blood transfusion may adversely impact graft longevity.

Incidence, Predictors, and Mortality of Infective Endocarditis in Adults With Congenital Heart Disease Without Prosthetic Valves.

Congenital heart disease (CHD) increases the risk of infective endocarditis (IE), though the lesion-specific risk and mortality are poorly defined. Using the population-based Quebec CHD database, we sought to describe the predictors of IE and to evaluate if IE was associated with mortality among adult CHD (ACHD) patients without prior valve replacement surgery. We extracted data on ACHD patients with IE and assessed the lesion-specific incidence of IE, risk factors for IE acquisition, and all-cause 1-year mortality. Among 29,866 ACHD patients, 285 (0.95%) developed IE during follow-up period of 378,901 patient-years, from 1988-2010. The highest and lowest lesion-specific incidences of IE were observed with left-sided lesions (1.61/1000 patient-years) and patent ductus arteriosus (0.24/1000 patient-years), respectively. The following predicted the risk of IE acquisition (odds ratio (OR), 95% confidence interval [CI]): cardiac surgery in the previous 6 months (9.07, 3.98-20.67), endocardial cushion defects (6.65, 3.84-11.53), left-sided lesions (5.11, 3.60-7.25), cyanosis at birth (4.82, 3.12-7.46), ventricular septal defect (2.81, 1.87-4.21), diabetes mellitus (1.65, 1.10-2.48), and recent medical interventions (12.52, 5.23-29.97). Twenty-five (8.77%) patients died within 1-year of IE diagnosis, a substantially elevated rate compared to patients without IE (OR 31.07, 95%CI 16.23-59.49). The risk of death following IE diagnosis was similarly elevated among patients with left-sided, cyanotic and other CHD lesions. In conclusion, the risk of IE in ACHD patients is lesion-specific and is greatest in the context of recent medical interventions. IE is associated with increased 1-year mortality, irrespective of broad CHD lesion grouping.

Aortic Dilatation at Different Levels of the Ascending Aorta in Patients with Bicuspid Aortic Valve.

INTRODUCTION: Bicuspid aortic valve (BAV) is the most common form of adult congenital heart disease. When compared to patients with a normal trileaflet aortic valve, dilatation of the aortic root and the ascending aorta (Asc Ao) are the common findings in patients with BAV, with consequent higher risk of developing aortic aneurysm, aortic dissection and rupture. We aim to determine the site of the Asc Ao where maximum dilatation occurs in Asian adult patients with BAV. MATERIALS AND METHODS: All subjects underwent full echocardiography examination. The diameter of the Asc Ao was measured at 3 cm, 4 cm, 5 cm, 6 cm and 7 cm from the level of aortic annulus to the Asc Ao in 2D from the parasternal long-axis view. RESULTS: A total of 80 patients (male/female: 45/35; mean age: 45.3 ± 16.2 years) with congenital BAV and 30 normal control group (male/female: 16/14; mean age: 45.9 ± 15.1 years) were enrolled. The indexed diameters of the Asc Ao were significantly larger than the control group. In patients with BAV, maximum dilatation of Asc Ao occurred around 6 cm distal to the aortic annulus. CONCLUSION: In patients with BAV, dilatation of Asc Ao is maximal at the mid Asc Ao region around 6 cm distal to the aorta annulus.

Surgical correction of persistent truncus arteriosus on a 33-year-old male with unilateral pulmonary hypertension from migration of pulmonary artery band.

BACKGROUND: Persistent truncus arteriosus is a rare congenital condition with which survival into adulthood is dismal without surgery. This is the oldest patient reported to our knowledge demonstrating the feasibility of assessing operability in persistent truncus arteriosus with unilateral pulmonary stenosis, and performing full corrective surgery in adulthood. CASE PRESENTATION: We report a Chinese male with successful correction of Type I persistent truncus arteriosus at 33 years of age. He had unilateral pulmonary hypertension from migration of pulmonary artery band from the main to the right pulmonary artery, severe truncal valve regurgitation from previous infective endocarditis, and progressive congestive heart failure. Improvement of lung perfusion was demonstrated 21 months post operation. CONCLUSION: This case demonstrated that in patients with persistent truncus arteriosus and two pulmonary arteries, pulmonary vascular disease or underdevelopment of one lung does not preclude a full corrective surgery so long as the other vascular bed is normal. It is important to emphasize the importance of assessing patient's operability in totality.

Cardiac MRI based numerical modeling of left ventricular fluid dynamics with mitral valve incorporated.

Recent numerical studies were focused on the modeling of flow in patient-specific left ventricle (LV); however, the mitral valve (MV) was usually excluded. In this study, both patient-specific LV and MV were modeled to achieve a more realistic intraventricular flow. Cardiac MRI images were acquired from a pulmonary arterial hypertension (PAH) patient and a healthy volunteer, and manual segmentation was conducted to reconstruct three-dimensional (3D) LV and MV geometries at each frame. Based on these 3D geometries, vortex formation time (VFT) was derived, and the values were 4.0 and 6.5 for the normal subject and the PAH patient, respectively. Based on studies in the literature, VTF in the healthy subject fell within the normal range, while that in the PAH patient exceeded the threshold for normality. The vortex structures in the LV clearly showed that the vortex ring was initiated from the tips of the MV instead of the mitral annulus. The excessive VFT during the rapid filling phase in the PAH patient resulted in a trailing flow structure behind the primary vortex ring, which was not observed in the normal subject. It can be deduced from this study that incorporating the MV into a patient-specific model is necessary to produce more reasonable VFT and intraventricular flow.

Cardiac output as a predictor in congenital heart disease: Are we stating the obvious?

BACKGROUND: Significant pulmonary regurgitation, declining right-sided ejection fraction, increased right ventricular (RV) volumes as well as left ventricular (LV) dysfunction have all been identified as predictors of poor outcomes in patients with congenital heart disease (CHD). The prognostic value of the cardiac output (CO) in these patients however has never been studied. METHODS: All consecutive ambulatory adult patients with CHD referred for magnetic resonance imaging (MRI) at the Montreal Children's Hospital between June 2007 and May 2009 were included. Right ventricular (RV) and left ventricular (LV) variables including end diastolic and end systolic volumes (EDV, ESV respectively), ejection fractions (EF) and regurgitant volumes were obtained. Cardiac index (CI) was calculated. Patients were followed for cardiac-related hospitalizations and cardiac interventions. RESULTS: Ninety-six patients were included. Median follow up was 3.9 ± 1.4 years. Nineteen percent of patients had a systemic CI<2.4 l/min/m(2). LVEDV, LVEF and RVEF were significantly diminished in the low CI group with a significant increase in RVESV and total regurgitant volume. Best predictors of low CI were LVEF (AUC=0.74), RVEF (AUC=0.71), total RV regurgitant volume (AUC=0.64) and RVESV (AUC=0.563). Low systemic CI was the best predictor of cardiac-related hospitalizations (hazard ratio 3.5, 95% confidence interval 1.5-8.5) and cardiac interventions (hazard ratio 2.2, 95% confidence interval 1.3-4.0), superior to LVEF, RVEF, total regurgitant volume and RVESV parameters. CONCLUSIONS: In patients with congenital heart disease, cardiac index is the best predictor of cardiac hospitalizations and cardiac interventions.

Molecular pathogenesis of Marfan syndrome.

Marfan syndrome (MFS) is a genetic disorder that affects multiple organs. Mortality imposed by aortic aneurysm and dissections represent the most serious clinical manifestation of MFS. Progressive pathological aortic root enlargement as the result of degeneration of microfibril architecture and consequential loss of extracellular matrix integrity due to fibrillin-1 (FBN1) mutations are commonly diagnosed clinical manifestations of MFS. However, overlapping clinical manifestations with other aneurysmal disorders present a significant challenge in early and accurate diagnosis of MFS. While FBN1 mutations, abnormal transforming growth factor-ß signaling and dysregulated matrix metalloproteinases have been implicated in MFS, clinically accepted risk-stratifying biomarkers have yet to be reliably identified. In this review, we summarize current consensus and recent insights in the understanding of MFS pathogenesis. Finally, we introduce the application of induced pluripotent stem cells (iPSCs) as cellular models for MFS and its potential as a novel platform into providing better appreciation of mechanisms underlying MFS diverse manifestations in the cardiovascular system.

Anatomical considerations for the development of a new transcatheter aortopulmonary shunt device in patients with severe pulmonary arterial hypertension.

Abstract Morbidity from pulmonary arterial hypertension (PAH) ensues when the pulmonary pressure reaches suprasystemic levels. A transcatheter alternative to the Potts shunt would allow decompression of the right heart without the surgical risks. To aid development of a transcatheter aortopulmonary shunt (TAPS) device, we described the anatomic relationship between the left pulmonary artery (LPA) and the descending aorta (dAO) in adults with severe pulmonary hypertension. Adults with severe PAH (peak systolic pulmonary arterial pressure [PASP] ≥80 mmHg) who had computed tomography of the chest were enrolled. Measurements were taken on the axial plane at the level of the pulmonary artery bifurcation. Forty patients (male sex, 9 patients; median age ± standard deviation [SD], [Formula: see text] years; median PASP ± SD, [Formula: see text] mmHg) were identified. The mean distance (±SD) between the LPA and dAO was [Formula: see text] mm. The mean luminal dAO and LPA diameters (±SD) were [Formula: see text] mm and [Formula: see text] mm, respectively. The LPA and dAO approximated in 93% of patients, with 38% having aortic calcification at the contact site. The mean "landing zone" width and height (defining an area with distance <4 mm between the outer borders) of the two arteries were [Formula: see text] mm and [Formula: see text] mm, respectively, at a mean distance of [Formula: see text] mm from the main pulmonary artery bifurcation. This study shows that the landing zone is able to accommodate a TAPS device of up to 15 mm in diameter in the majority of patients with severe PAH.

Trans-pleural pericardiocentesis: revisiting an old technique.

Percutaneous access to the pericardial space serves both diagnostic and therapeutic purposes. Multiple approaches have been described, which include the apical, sub-xiphoid, trans-atrial, and trans-bronchial techniques. Occasionally, in the presence of both left pleural effusion and posterior pericardial effusion, echocardiographically guided pleuropericardial drainage can be carried out using the left axillary approach. Here we revisit the use of this technique in a patient. Future development of this technique, using a noncompliant balloon to expand the pleuropericardial interface, may avoid the need for a pericardial window in oncology and rheumatology patients with recurrent pericardial effusions.

Management of antiplatelet therapy during acute percutaneous coronary intervention: new strategies and therapeutics.

Aggressive intravenous and oral dual antiplatelet therapy has established primary percutaneous coronary intervention (PCI) as the standard of care for acute myocardial infarction. Clopidogrel is currently the thienopyridine of choice for dual antiplatelet therapy in patients treated with PCI. The dose regime and duration of therapy of clopidogrel has undergone multiple refinements. Recently, 2 novel third generation oral inhibitors of P2Y12 receptors, prasugrel and ticagrelor, have undergone clinical evaluation with promising results. This article is a non-exhaustive review of the literature, concentrating on the role of current and novel oral antiplatelet agents for acute myocardial infarction particularly highlighting the limitations and issues associated with clopidogrel use.