Bio

Clinical Focus


  • Pediatric Cardiology - Noninvasive Imaging
  • Pediatrics
  • General Pediatric Cardiology

Academic Appointments


Professional Education


  • Board Certification: Pediatrics, American Board of Pediatrics (2005)
  • Residency:The Hospital for Sick Children (2008) Canada
  • Board Certification, Subspecialty: Pediatric Cardiology, American Board of Pediatrics (2012)
  • Fellowship:Children's Hospital Boston (2012) MA
  • Internship:The Hospital for Sick Children (2006) Canada
  • Medical Education:Queens University (2005) ONCanada

Publications

Journal Articles


  • Transcatheter Device Closure of a Congenital Aortic-Left Atrial Tunnel CONGENITAL HEART DISEASE Sun, H. Y., Buccola, K. J., Punn, R., Silverman, N. H., Peng, L. F., Perry, S. B., Balasubramanian, S. 2014; 9 (1): E23-E26

    Abstract

    Rare cases of aortic-left atrial tunnel exist in the literature. This case report highlights the echocardiographic characterization of this vascular anomaly and provides the first description of an aortic-left atrial tunnel closed by interventional cardiac catheterization in a pediatric patient.

    View details for DOI 10.1111/chd.12059

    View details for Web of Science ID 000329916300010

    View details for PubMedID 23601836

  • Chest Radiographic Findings in Pediatric Patients with Intraluminal Pulmonary Vein Stenosis. Congenital heart disease Mayhew, C. E., Lee, E. E., Balasubramanian, S., Muneeb, M., Gauvreau, K., Tracy, D. A., Jenkins, K. J. 2013

    Abstract

    Early recognition of pulmonary vein stenosis (PVS) is crucial for optimizing clinical outcomes. Our goal was to characterize radiographic patterns specific to pediatric patients with PVS to facilitate early detection. PATIENTS AND METHODS: Pediatric patients with multivessel (?2) intraluminal PVS were identified from a single-center registry. Initial chest radiographs were reviewed. Radiographic findings were summarized using frequencies and percentages for categorical data, and medians and ranges for continuous data. Interrater agreement was assessed using kappa statistics. RESULTS: Chest radiographs of 41 PVS patients were evaluated; median age at presentation 5.2 (0.5-102.6) months. Underlying congenital heart disease was present in 31 (76%), lung disease in four (10%), and neither in six (15%). Common heart diseases were hypoplastic left heart syndrome (five, 12%), totally anomalous pulmonary venous connection (nine, 22%), and heterotaxy (five, 12%). PVS was bilateral in 22 (54%), right-sided in six (14%), and left-sided in 13 (32%). All chest radiographs were abnormal. Increased interstitial opacity was present in all patients, reticular opacity in 35 (85%), and ground-glass opacity in 29 (71%). Consolidation (one, 2%), pleural effusions (four, 10%), and nodular opacities (0) were unusual. Distributional heterogeneity was common (17, 42%). Interrater agreement was generally high (kappa >0.84) except for lobe location. Findings were similar among patients with isolated PVS, PVS with congenital heart disease, and PVS with lung disease. CONCLUSION: Diagnosis of PVS should be considered in infants with increased interstitial opacity, reticular opacity, and ground-glass opacity on chest radiography, especially if findings are heterogeneous.

    View details for PubMedID 23773478

  • Midgestation Fetal Pulmonary Annulus Size Is Predictive of Outcome in Tetralogy of Fallot. Congenital heart disease Friedman, K., Balasubramanian, S., Tworetzky, W. 2013

    Abstract

    Surgical management of tetralogy of Fallot (TOF) is increasingly moving toward valve-sparing approaches rather than transannular patch (TAP). We evaluate whether fetal pulmonary valve (PV) size is predictive of postnatal course and surgical approach in TOF.In this retrospective study, fetal and postnatal demographic, clinical, and echocardiographic data on 66 patients diagnosed prenatally with TOF were collected. We compared those with midgestation PV?z-score > -3.5 to those with z-score ?-3.5. We analyzed fetal and postnatal PV size and growth and outcomes between groups RESULTS: Gestational age at first fetal echo was 23 weeks (range 18-28). PV diameter and z-score on midgestation echo were 3.5?mm (1.3-6.0) and -2.8 (-0.5 to -6.0) respectively. Patients with PV?z-score ? -3.5 on first fetal echo had smaller PV diameter (4.5 vs. 5.0?mm, P = .047) and PV?z-score (-3.8 vs. -2.8, P < .001) in late gestation and at time of surgery (6.0?mm vs. 7.0?mm, P = .01; z-score = -2.9 vs. -1.7, P = .007). Similarly, those with smaller fetal PV?z-score had smaller main and branch pulmonary arteries at time of surgery. PV growth rate over gestation was similar between groups, while after-birth PV growth rate was lower in those with smaller PV (0?mm/month vs. 0.6?mm/month, P = .002). Those with smaller pulmonary valve were more likely to be cyanotic (P = .05), to undergo surgery at <1 month (P < .01), and to have a TAP repair (P = .01). Among patients undergoing valve-sparing repair, those with smaller PV underwent more reinterventions for residual valvar PS (P < .01).Midgestation fetal PV size is predictive of postnatal PV and PA size in TOF. Midgestation PV size has implications for timing and type of surgical management as well as for need for reintervention in valve-sparing repair patients and is therefore important to consider in prenatal counseling for TOF fetuses.

    View details for PubMedID 23834770

  • Bilateral Disease and Early Age at Presentation Are Associated with Shorter Survival in Patients with Congenital Heart Disease and Intraluminal Pulmonary Vein Stenosis CONGENITAL HEART DISEASE Balasubramanian, S., Rehman, M., Gauvreau, K., Jenkins, K. J. 2012; 7 (4): 378-386

    Abstract

    Pulmonary vein stenosis (PVS) is a progressive disease that is frequently lethal. We have previously identified neoproliferation of myofibroblasts as the mechanism for progressive intraluminal PVS. PVS occurs in association with other congenital heart diseases (CHD) and in structurally normal hearts. This study sought to describe the spectrum of CHD seen with PVS and explore risk factors associated with mortality.All patients diagnosed over a 12-year period with a combination of PVS involving ?2 vessels and CHD were identified. Cases were categorized according to major anatomic and physiologic categories. Patient and disease characteristics associated with time to death were explored.Eighty-two cases followed longitudinally at our institution were analyzed. Anatomic diagnoses included nonheterotaxy + anomalous pulmonary venous return (29%), heterotaxy + anomalous veins (20%), two ventricles + normal veins (22%), and single ventricle + normal veins (29%). Median age at diagnosis was 5.3 months (0-24 years). Despite multiple treatments, there were 35 (43%) deaths in the group with an estimated survival of 71%, 64%, and 44% at 1, 2, and 5 years, respectively. Bilateral disease at diagnosis (hazard ratio [HR] 3.9 [1.7, 9.2], P= .002), age <5 months at diagnosis (HR 3.4 [1.6, 7.6], P= .002), and involvement of >2 pulmonary veins at diagnosis (HR 3.7 [1.6, 8.8], P= .003) were associated with shorter time to death in univariate analysis. In multivariable analysis, both bilateral disease (HR 2.9 [1.2, 7.1]P= .02) and age <5 months at diagnosis (HR 2.4 [1.1, 5.6]P= .03) were independently associated with time to death.Bilateral disease and earlier age at diagnosis are independent predictors of poor survival in patients with CHD and PVS, while patients with unilateral disease presenting at an older age have a better prognosis. These findings are helpful in risk stratification of patients with CHD and multivessel PVS.

    View details for DOI 10.1111/j.1747-0803.2012.00647.x

    View details for Web of Science ID 000306761200017

    View details for PubMedID 22469299

  • Outcomes After Stent Implantation for the Treatment of Congenital and Postoperative Pulmonary Vein Stenosis in Children CIRCULATION-CARDIOVASCULAR INTERVENTIONS Balasubramanian, S., Marshall, A. C., Gauvreau, K., Peng, L. F., Nugent, A. W., Lock, J. E., McElhinney, D. B. 2012; 5 (1): 109-117

    Abstract

    Pulmonary vein stenosis (PVS) is a rare condition that can lead to worsening pulmonary hypertension and cardiac failure in children, and it is frequently lethal. Surgical and transcatheter approaches are acutely successful but restenosis is common and rapid.We reviewed outcomes among patients who underwent transcatheter pulmonary vein stent implantation for congenital or postoperative PVS at <18 years of age. A total of 74 pulmonary veins were stented with bare metal, drug-eluting, or covered stents in 47 patients. Primary diagnoses included PVS associated with anomalous venous return in 51%, PVS associated with other congenital cardiovascular defects in 36%, and congenital ("de novo") PVS in 13% of patients. Median age at the time of pulmonary vein stent implantation was 1.4 years. During a median cross-sectional follow-up of 3.1 years, 21 patients died. Estimated survival was 62▒8% at 1 year and 50▒8% at 5 years after pulmonary vein stent implantation. Stent placement acutely relieved focal obstruction in all veins. Of the 54 stents reexamined with catheterization, 32 underwent reintervention. Freedom from reintervention was 62▒7% at 6 months and 42▒7% at 1 year. Stent occlusion was documented in 9 cases and significant in-stent stenosis in 17 cases. Stent implantation diameter ?7 mm was associated with longer freedom from reintervention (hazard ratio, 0.32; P=0.015) and from significant in-stent stenosis (hazard ratio, 0.14; P=0.002). Major acute complications occurred in 5 cases.Transcatheter stent implantation can acutely relieve PVS in children, but reintervention is common. Larger stent lumen size at implantation is associated with longer stent patency and a lower risk of reintervention.

    View details for DOI 10.1161/CIRCINTERVENTIONS.111.964189

    View details for Web of Science ID 000300610900021

    View details for PubMedID 22253356

  • Human immunodeficiency virus-1 infection protects against a Tc1-to-Tc2 shift in CD8(+) T cells HUMAN IMMUNOLOGY Gulzar, N., Diker, B., Balasubramanian, S., Jiang, J. Q., Copeland, K. F. 2011; 72 (11): 995-1000

    Abstract

    Despite the reports of dysfunction of the lytic abilities of CD8(+) T cells during human immunodeficiency virus-1 (HIV-1) disease progression, the effects of infection on the noncytolytic functions of CD8(+) T cells have not been well characterized to date. We examined the effect of HIV-1 infection on the cytokine and chemokine responses of peripheral blood-derived CD8(+) T cells in an in vitro system. Activation of HIV-1-infected CD8(+) T cells with phytohemagglutinin resulted in a 4- to 8-fold increase in the production of macrophage inflammatory protein (MIP)-1?, MIP-1?, regulated on activation normal T-cell expressed and secreted, and interleukin (IL)-16. Treatment of activated HIV-1-infected CD8(+) T cells with anti-CD3 monoclonal (M) antibody (Ab) and IL-15 induced strong production of interferon-? (IFN-?). Treatment of cells with anti-IL-12 MAb and IL-4 to induce a Tc1-to-Tc2 shift resulted in no change in viral production levels or IFN-? production within the HIV-1-infected CD8(+) T cell population. Initiation of a Tc2-to-Tc1 shift resulted in a 6-fold increase in HIV-1 replication and 2- to 3-fold higher levels of IFN-?, demonstrating that infection can protect against a Tc1-to-Tc2 shift in CD8(+) T cells.

    View details for DOI 10.1016/j.humimm.2011.08.012

    View details for Web of Science ID 000296546100001

    View details for PubMedID 21920400

  • Infection of CD8+CD45RO+ memory T-cells by HIV-1 and their proliferative response. The open AIDS journal Gulzar, N., Balasubramanian, S., Harris, G., Sanchez-Dardon, J., Copeland, K. F. 2008; 2: 43-57

    Abstract

    CD8+ T-cells are involved in controlling HIV-1 infection by eliminating infected cells and secreting soluble factors that inhibit viral replication. To investigate the mechanism and significance of infection of CD8+ T-cells by HIV-1 in vitro, we examined the susceptibility of these cells and their subsets to infection. CD8+ T-cells supported greater levels of replication with T-cell tropic strains of HIV-1, though viral production was lower than that observed in CD4+ T-cells. CD8+ T-cell infection was found to be productive through ELISA, RT-PCR and flow cytometric analyses. In addition, the CD8+CD45RO+ memory T-cell population supported higher levels of HIV-1 replication than CD8+CD45RA+ na´ve T-cells. However, infection of CD8+CD45RO+ T-cells did not affect their proliferative response to the majority of mitogens tested. We conclude, with numerous lines of evidence detecting and measuring infection of CD8+ T-cells and their subsets, that this cellular target and potential reservoir may be central to HIV-1 pathogenesis.

    View details for DOI 10.2174/1874613600802010043

    View details for PubMedID 18923697

  • Pulmonary vein stenosis: expression of receptor tyrosine kinases by lesional cells CARDIOVASCULAR PATHOLOGY Riedlinger, W. F., Juraszek, A. L., Jenkins, K. J., Nugent, A. W., Balasubramanian, S., Calicchio, M. L., Kieran, M. W., Collins, T. 2006; 15 (2): 91-99

    Abstract

    Primary pulmonary vein stenosis (PVS) is a progressive disorder of infants. Although catheter based intervention and chemotherapy are used to manage the disorder, the benefit of these approaches is reduced considerably by restenosis. The nature of the intimal cells causing the occlusive lesions in PVS is poorly understood.Seven PVS cases were studied with antibodies for smooth muscle actin (SMA), muscle-specific actin (MSA), monoclonal desmin, S100 protein, CD31, CD34, CD45RO, CD68, CD99, Ki-67 (MIB-I), and with antibodies directed against several receptor tyrosine kinases (RTK), including platelet-derived growth factor alpha and beta receptor (PDGFR-alpha and -beta), epidermal growth factor receptor (EGFR), fibroblast growth factor receptor (FGFR), vascular endothelial growth factor 1 and 2 receptor (VEGFR), and stem cell factor receptor (c-kit).Lesional cells stained strongly and diffusely with SMA and MSA, but not for macrophage, lymphocyte, endothelial markers, or for Ki-67. RTK expression was strong and diffuse for PDGFR-alpha and -beta, FGFR, and VEGFR-2. Lesional cells stained for VEGF and PDGF beta receptor was phosphorylated.The histologic appearance, and the strong diffuse immunoreactivity for smooth muscle markers, indicates that the intimal lesional cells are myofibroblast-like. Expression of various receptor tyrosine kinases and some ligands suggests an autocrine or paracrine role of these proteins in the pathogenesis of the intimal occlusive lesion in PVS.

    View details for DOI 10.1016/j.carpath.2005.11.006

    View details for Web of Science ID 000236664600004

    View details for PubMedID 16533697

  • Pediatric surgeons and pediatric emergency physicians' attitudes towards analgesia and sedation for incarcerated inguinal hernia reduction JOURNAL OF PAIN Goldman, R. D., Balasubramanian, S., Wales, P., Mace, S. E. 2005; 6 (10): 650-655

    Abstract

    Inguinal hernias become incarcerated in 10% to -15% of children and reduction of the hernia is an urgent painful procedure. No recommendations exist for analgesia during this procedure. We surveyed pediatric emergency physicians (PEP) and pediatric surgeons (PS) for their analgesia and sedation use during the reduction. The survey was mailed to 19 centers in North America. A total of 56% (185/331) surveys were completed by PEP and 56% (68/122) from PS. A total of 96.7% (245/253) of responders reported giving analgesia or sedation during reduction. PS were more likely to use intravenous drugs, try for a longer time, wait longer between trials, and conduct more trials compared to the PEP. Clinically related variables were more important for PEPs than PS for analgesia and sedation. System-related variables were more important by PS for admission.This survey shows significant variability between specialties in the drugs, route, and number of attempts during reduction of a painful incarcerated hernia in children. Development of a sedation and analgesia protocol may be useful in order to unify management of pain and discomfort during hernia reduction.

    View details for DOI 10.1016/j.jpain.2005.05.001

    View details for Web of Science ID 000232786600003

    View details for PubMedID 16202957

  • Topical nonsteroidal anti-inflammatory drugs for corneal abrasions: Meta-analysis of randomized trials ACADEMIC EMERGENCY MEDICINE Calder, L. A., Balasubramanian, S., Fergusson, D. 2005; 12 (5): 467-473

    Abstract

    To determine the effectiveness of topical nonsteroidal anti-inflammatory drugs (NSAIDs) in traumatic corneal abrasions.This was a systematic literature review and meta-analysis of randomized clinical trials (RCTs). The following databases were searched: MEDLINE (1966-2004), EMBASE (1980-2004), and Cochrane Central Register of Controlled Trials and Database of Systematic Reviews (first quarter 2004). The structured search strategy included a RCT filter and the terms "cornea," "wounds and injuries," "trauma," "corneal diseases," "eye injuries," "anti-inflammatory agents, nonsteroidal" and specific trade names of topical NSAIDs. In addition, four journals in ophthalmology and emergency medicine were hand searched. Two authors independently reviewed citations from the literature searches. To be included, studies had to be RCTs evaluating topical NSAIDs in traumatic corneal abrasions. Trials were included regardless of language or whether they were unpublished or published. Exclusion criteria were corneal ulcers, nonrandomized studies, animal studies, or perioperative setting. Outcomes were pain scale scores at 24 hours and adverse effects. Two independent reviewers assessed four trial quality components: randomization, double blinding, reporting of withdrawals, and concealment of allocation. Weighted mean difference, using a random effects model, was calculated.Of the 200 citations identified, 11 RCTs met inclusion criteria. Eight trials were identified from the MEDLINE search, two from the EMBASE search, and one from conference proceedings. Seven trials enrolled fewer than 100 patients, and more than half of the studies were conducted in Europe. Five trials reported suitable data for analysis. The overall weighted mean difference for 459 patients was a reduction in pain by 1.30 points (95% confidence interval = -1.56 to -1.03) on the pain scale. Five of the trials met criteria for good quality. Transient stinging was a commonly noted adverse effect.Topical NSAIDs are effective analgesics for traumatic corneal abrasions.

    View details for Web of Science ID 000228817100014

    View details for PubMedID 15860701

  • Lack of consensus on corneal abrasion management: results of a national survey. CJEM Calder, L., Balasubramanian, S., Stiell, I. 2004; 6 (6): 402-407

    Abstract

    Our objective was to determine the practice patterns of Canadian emergency physicians with respect to the management of traumatic corneal abrasions.After developing our instrument and pilot testing it on a sample of emergency residents, we randomly surveyed 470 members of the Canadian Association of Emergency Physicians, using a modified Dillman technique. We distributed a pre-notification letter, an 18-item survey, and appropriate follow-up surveys to non-responders. Those members with an email address (n = 400) received a Web-based survey, and those without (n = 70) received a survey by post. The survey focused on the indications and utilization of analgesics (oral and topical), cycloplegics, eye patches and topical antibiotics.Our response rate was 64% (301/470), and the median age of respondents was 38 years. Most (77.7%) were male, 71.8% were full-time emergency physicians, 76.5% were emergency medicine certified, and 64.4% practised in teaching hospitals. Pain management preferences (offered usually or always) included oral analgesics (82.1%), cycloplegics (65.1%) and topical non-steroidal anti-inflammatory drugs (NSAIDs) (52.8%). Only 21.6% of respondents performed patching, and most (71.2%) prescribed topical antibiotics, particularly for contact lens wearers and patients with ocular foreign bodies. Two-thirds of the respondents provided tetanus toxoid if a foreign body was present, and 46.2% did so even if a foreign body was not present. Most respondents (88.0%) routinely arranged follow-up.This national survey of emergency physicians demonstrates a lack of consensus on the management of traumatic corneal abrasions. Further study is indicated to determine the optimal treatment, particularly regarding the use of topical NSAIDs.

    View details for PubMedID 17378958

  • Production of CD8(+) T cell nonlytic suppressive factors by CD28, CD38, and HLA-DR subpopulations AIDS RESEARCH AND HUMAN RETROVIRUSES Jiang, J. Q., Balasubramanian, S., Hawley-Foss, N. C., Badley, A. D., Rosenthal, K. L., Copeland, K. F. 2003; 19 (6): 497-502

    Abstract

    HIV infection may be modified by CD8(+) T cells by the production of nonlytic antiviral factors. To determine subpopulations that mediate nonlytic, antiviral activity, we examined the production of beta chemokines and of CD8 antiviral factor (CAF) by different subsets, using CD8(+) cells derived from 24 HIV-1-infected and 25 uninfected individuals. Subjects with CD8(+) cell counts greater than 200/microl produced increased levels of MIP-1alpha by CD8(+)CD28(+), CD8(+)CD38(-), and CD8(+)HLA-DR(+) subsets as compared with uninfected controls. CD8(+)CD38(-) cells produced higher levels of MIP-1beta and RANTES. CAF production was increased by CD8(+)CD38(+) and CD8(+)HLA-DR(+) cells of HIV-infected individuals as compared with uninfected controls. Chemokine production was increased by cells that do not express activation markers, whereas CAF activity was increased by cells expressing CD38 or HLA-DR. These findings shed light on CD8(+) T cell noncytotoxic antiviral factor production during HIV infection.

    View details for Web of Science ID 000184055500008

    View details for PubMedID 12882659

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