Ongoing Research

Echocardiography (ultrasound of the heart):

Echocardiography is used to assess heart anatomy and function, as well as indirectly assessing the pulmonary artery pressures (pulmonary blood pressure). It is a powerful tool giving live insight into hemodynamic conditions. Speckle tracking echocardiography (STE) assesses cardiac function by quantifying change in muscle length (strain) and the speed at which it occurs (strain rate). STE uses routine grayscale speckle patterns from frame to frame to derive quantitative regional functional data in order to analyze regional wall function. STE allows a better assessment of the systolic (contraction) and diastolic (relaxation) mechanics of the right and left ventricle (cardiac chambers). Furthermore, differences of rotational mechanics between the basal (clockwise rotation as viewed from apex) and the apical (counterclockwise rotation as viewed from apex) of the left ventricle allows for evaluation of twisting cardiac deformation.

Near infrared spectroscopy (NIRS):

NIRS has been used as a non-invasive real-time modality for monitoring cerebral and renal oxygenation and perfusion. Regional cerebral oxygen saturation (measured at the level of the frontal cortex) correlates with cerebral perfusion and lower cerebral saturations have been associated with adverse neurological outcomes and ischemic anomalies on imaging in specific neonatal populations. In my work at Stanford, we showed that decreased abdominal aortic blood flow was associated with decreased values of renal saturations, an indicator of poor distal perfusion. Cerebral NIRS has been correlated with the incidence of intraventricular hemorrhage and periventricular leukomalacia, and has been reported as a surrogate for the presence of a hemodynamically significant patent ductus arteriosus (PDA)

My research interests are in:

a) Pulmonary vascular disease and right ventricular function in the immediate neonatal period, in the context of:

a. Extreme prematurity and bronchopulmonary dysplasia

b. Post-natal disturbances in adaptation (hypoxic ischemic injury or sepsis)

c. Congenital cardiac defects

d. Congenital/Neonatal pulmonary lesions such as congenital diaphragmatic hernia or meconium aspiration syndrome

b) Mid- and long-term consequences of pulmonary vascular disease and right ventricular remodeling during the neonatal period, and its impact during pediatric and adult life.

The goals of my research:

By gaining a better understanding of the natural history and outcomes of neonatal patients with hemodynamic compromise related to pulmonary vascular disease, my hope is to intervene early enough to prevent poor cardiac and neurological outcomes in this growing patient population. Although limited data exists, prematurity and neonatal pathologies have been associated with adverse pediatric and adult outcomes. We have not yet determined the cardiac behaviors of infants born prematurely. There is also growing evidence that newborns with pulmonary vasculature injury have persistent compromise in their cardiac and pulmonary function. Limited data exists on the natural history or interventions to improve the cardiac care of premature newborns. I wish to improve our understanding in order to offer better care to the neonatal population.

Congenital diaphragmatic hernia (CDH):

CDH still carries a high mortality and morbidity burden. In this defect, hypoxic respiratory failure is compounded by hemodynamic instability. iNO is effective in term and near-term infants to reduce the incidence of extracorporeal membrane oxygenation (ECMO) or death in newborns with hypoxic respiratory failure associated with echocardiographic or clinical evidence of persistent pulmonary hypertension of the newborn (PPHN). By using iNO in the CDH population, the hope was to reversethe increased vascular tone, in order to improve survival and decrease ECMO use. However, multiple studies have failed to document a benefit of inhaled nitric oxide (iNO) in the CDH population. Focus has been put for many years on the evaluation and management of high pulmonary vascular resistance and the resultant pulmonary hypertension. Recently, my work at Stanford University with a CDH population showed that decreased LV and RV function, as assessed by standard and speckle tracking echocardiography measures, was associated with need for ECMO. There was no difference in rates of pulmonary hypertension between patients receiving ECMO and those who did not. Pulmonary arterial vasodilators are contra-indicated in the setting of decreased left ventricular function and in other conditions leading to pulmonary venous congestion and post-capillary pulmonary hypertension. My hypothesis is: abnormal cardiac function may explain the non-response to pulmonary arterial vasodilators such as iNO in CDH patients, and through more detailed assessment of their cardiac function, we will tailor our therapy to provide better hemodynamic support. My future research will use echocardiographic tools to identify at risk CDH patients with cardiac failure in order to introduce appropriate therapy to support cardiac function (such as milrinone which has lusitropic properties). Echocardiography will then be used to follow CDH patients in real time and to confirm response to therapy. Thus, my research will surround the identification of patients at risk and the management strategies to improve cardiac function. As well, no data exists about long term cardiac outcomes in the CDH population and my future research will focus on long term cardiovascular assessments of this population.

Bronchopulmonary dysplasia (BPD):

Pulmonary vascular disease (PVD) and the resultant pulmonary hypertension (PH), as well as BPD are common complications in the extremely premature population [3]. Several mechanistic factors predispose towards development of PVD such as vascular remodelling, reduced vascular density and surface area, and increased vascular tone and reactivity. Physiologically, the end result is an increase in pulmonary vascular resistance translating in an elevated pulmonary artery pressure that can lead to right ventricle (RV) hypertrophy and occasionally RV failure. PH and BPD are linked, but separate, entities. Indeed, some patients with severe BPD phenotype have normal pulmonary vascular pressures and right heart function [4]. Conversely, although much less frequently, infants with no or mild BPD demonstrate severe PH and RV failure. Mortality is severely impacted by the presence of PH. Indeed, in an infant population with BPD and PH diagnosed after 2 months of age, survival was of 64% ± 8% at 6 months and 53% ± 11% at 2 years after the diagnosis. In the same population, only 25% of the infants diagnosed with severe PH survived for more than 2 years after diagnosis. Furthermore, there have been reported cases of an association between BPD and pulmonary vein stenosis [6-8]. Limited data exists on the natural history of pulmonary hypertension in BPD, the best approach to management, and the cardiac prognosis. My hypothesis is that by gaining a better understanding of the natural history, as well as improved early detection, existing or new therapies could be applied at determinant times and within identified at-risk subgroups. This would prevent mid and long-term consequences of pulmonary vascular disease and right ventricular remodeling during the neonatal period.

Congenital heart defects (CHD):

Limited data exist on end-organ perfusion in neonates with CHD in the first days of postnatal life, with the fall of pulmonary vascular resistance (PVR). Goal-directed management of hypoperfusion and shock improves outcome in the pediatric and adult population. Near-infrared spectroscopy (NIRS) monitoring, as a surrogate of systemic and brain perfusion, may enhance the ongoing management of the CHD population starting from birth [9]. However, there are currently no strong correlation studies that link organ perfusion and NIRS readings. Additionally, there is no data confirming improved outcomes upon monitoring of NIRS in the pre-operative period in the CHD population. In an upcoming manuscript, my group described that in a population of single ventricles, descending aortic anterograde systolic flow VTI correlated with renal saturations, with a low VTI in the descending aorta corresponding to a lower renal saturation (p=0.02). Patients with a descending aorta systolic VTI < 0.05 meter (m) had significantly decreased renal saturations compared to those with VTI ≥ 0.05 m (Rsat 62±9 % vs 77±9 %, p=0.005). Besides this report, no studies have been published using live ultrasound / echocardiography markers as correlates with NIRS values to assess distal perfusion. My hypothesis is that subclinical cerebral and systemic hypoperfusion happens in the early post-natal period leading to poor outcomes, especially in the single ventricular population and those with ductal-dependent lesions. I wish to focus my future research on strategies to: 1) identify patients at risk of cerebral/systemic hypoperfusion upon drop of pulmonary vascular resistance in the first few post-natal days using NIRS, 2) validate the NIRS technique in the neonatal population by correlating NIRS values in the CHD group to echocardiographic markers of distal perfusion, as well asmarkers of cardiac function, 3) investigate the incidence of decreased left and/or right cardiac performance (assessed by echocardiography) as a key factor in the incidence of lower renal and/or cerebral saturations (NIRS), 4) optimize ongoing care using live NIRS measurement in CHD as a way to improve mid and long-term outcomes in this high-risk neonatal population.

The ultimate goal of my research:

By having a better understanding of the natural history and outcomes of neonatal patients with hemodynamic compromise related to pulmonary vascular disease, my hope is to eventually intervene early to prevent poor cardiac and neurological outcomes in this growing patient population. Although limited data exist, prematurity and neonatal pathologies have been associated with adverse pediatric and adult outcomes. We have not yet determined the cardiac behaviors of infants born prematurely. There is also growing evidence that newborns with pulmonary vasculature injury have persistent compromise in their cardiac and pulmonary function. Limited data exists on natural history or interventions to improve the cardiac care of premature newborns. I wish to improve our understanding in order to offer better care to the neonatal population.

Created by Gabriel Altit - Neonatologist / Créé par Gabriel Altit (néonatalogiste) - © NeoCardioLab