Ramkumar Krishnamurthy

Urine Albumin-to-Creatinine Ratio: A Marker of Early Endothelial Dysfunction in Youth

CONTEXT The urine albumin-to-creatinine ratio (UACR) is a useful predictor of cardiovascular (CV) events in adults. Its relationship to vascular function in children is not clear. OBJECTIVE We investigated whether UACR was related to insulin resistance and endothelial function, a marker of subclinical atherosclerosis, in adolescents across the spectrum of glucose regulation. PARTICIPANTS Participants were 58 adolescents: 13 normal weight (NW), 25 overweight with normal glucose tolerance (OW-NGT), and 20 overweight with prediabetes (OW-PreD). INTERVENTIONS Interventions included oral glucose tolerance test, hyperinsulinemic-euglycemic clamp with determination of insulin sensitivity (IS), endothelial function assessment by peripheral arterial tonometry determination of the reactive hyperemia index (RHI), body composition (dual-energy x-ray absorptiometry), and abdominal fat distribution (magnetic resonance imaging). PRIMARY OUTCOME MEASURE Fasting UACR was determined. RESULTS The 3 groups did not differ with respect to age, sex, or Tanner stage. The NW group had significantly lower percent body fat, higher IS (10.4 ± 0.9, 3.5 ± 0.6, and 2.1 ± 0.2 mg/kg/min per μU/mL; P < .001), and higher RHI (1.84 ± 0.1, 1.56 ± 0.1, and 1.56 ± 0.1, P = .04) than the OW-NGT and OW-PreD groups, respectively. lnUACR was related to percent body fat (r = 0.4, P = .001), RHI (r = -0.33, p = .01), and IS (r = -0.27, P = .043). In multiple regression analysis with lnUACR as the dependent variable and RHI, percent body fat, age, sex, race, systolic blood pressure, cholesterol, glycated hemoglobin, and IS as independent variables, RHI (β = -0.3, P = .045) and sex (β = 0.31, P = .06) contributed to the variance in UACR (R(2) = 0.35, P = .02). CONCLUSIONS UACR is an early marker of endothelial dysfunction in youth, independent of glycemia. Endothelial dysfunction may mediate the link between obesity-related insulin resistance and early microalbuminuria.

Mother's pre‐pregnancy BMI is an important determinant of adverse cardiometabolic risk in childhood

Maternal adiposity is associated with poor offspring cardiometabolic health. We aimed to evaluate the relationship of maternal pre‐pregnancy body mass index (BMI) on the BMI, body composition and cardiometabolic characteristics of the offspring.

Comparison of Respiratory-Triggered (RT) 3D cine steady-state free precession cardiac mri with standard 2D cine imaging and magnetic resonance angiography in Congenital Heart Disease (CHD).

Background This is a pilot study to evaluate the performance of whole-heart isotropic RT-3D cine SSFP sequence as an efficient single solution for assessment of morphology and function in CHD by comparing it to: 1. Short axis (SA) 2D cine SSFP for LV volumetry and function 2. Multiplanar 2D cine SSFP for intracardiac morphology 3. Cine 2D SSFP and gadolinium (Gd)-enhanced 3D MRA for aortic root size 4. Gd-3D MRA for vessel diameter (VD) 5. Gd-3D MRA, and cine 2D SSFP for morphology of extracardiac vasculature 6. Gd-3D MRA and multiplanar cine 2D SSFP for overall diagnosis.

Prospective comparison of circumferential and longitudinal strain in asymptomatic children with single left ventricle, single right ventricle and normal hearts

Background Ventricular dysfunction in patients with a single right ventricle (SRV) or as ingle left ventricle (SLV) is a known risk factor for morbidity and mortality. However, the differences in SRV and SLV function remain poorly understood, with only a few studies performed1-3. In this study, we measure the strain using cardiac MRI and perform comprehensive comparison of the global and regional strain in both the circumferential (ecc) and longitudinal (eL) dimension. Purpose: In normal subjects and asymptomatic patients with SLV and SRV after total cavopulmonary connection (TCPC), compare: 1) Global ecc and eL strain, 2) Regional circumferential and longitudinal strains at free wall (ecc-free, eL-free) and septum (ecc-sept, eL-sept), 3) ecc and eL across the ventricle from apex to base. Methods We performed a prospective analysis of 18 subjects (7 normal age: 11.8 +/- 3; 6 SRV age: 11.4 +/- 2.3; 5 SLV age: 12.7 +/- 4.2). Acquisition Protocol: Strain information was acquired at three short axis slices at basal, mid-cavity, and apical locations in all 18 subjects in a 1.5T MRI scanner (Philips Acheiva) using: a) Complementary Spatial Modulation of Magnetization (CSPAMM)4 images: Used for generating ecc; and b) Fast-Strain Encoded (fSENC)5 images: Used for generating eL. Data Analysis: ecc and eL across all cardiac phases and slices were calculated from SAX slices using DiagnosoftTM. The ventricular regions at each slice were assigned based upon the AHA 16 segment model. ecc-sept, eL-sept, ecc-free, and eL-free were also calculated for each slice and compared. Results

Ventricular coupling in single ventricle patients: a MRI study of cardiac biomechanics

Background Ventricular dysfunction in patients with a single right ventricle (SRV) or a single left ventricle (SLV) is a known risk factor for morbidity and mortality. In normal hearts, LV and RV augment each other, while this is not possible in single ventricle (SV) patients. Ventricular-ventricular relationship in SV patients remain poorly understood, with only a few studies performed [1-3]. Our earlier results show a decreased peak circumferential (εcc) and longitudinal (εL) strain in SV patients when compared to a normal population [4]. However, an increase in longitudinal strain is noted in regions of decreased circumferential strain. The purpose of this study is to understand the ventricular-ventricular interactions in systemic ventricles coupled and uncoupled to a dysfunctional ventricle.

Myocardial T1 mapping as a diagnostic tool in pediatric patients with a concern for cardiac disease

Background Myocardial tissue characterization with both native T1 mapping and T1 mapping following gadolinium based contrast agents (T1 enhanced) has emerged as an important asset of CMR imaging [1]. However, there is only minimal experience in pediatrics [2]. Native T1 has shown to be a marker of myocardial edema, and may play a role in pathologic states such as myocarditis [3]. T1 enhanced mapping has shown to be a useful biomarker for disease sates with diffuse fibrosis, such as hypertrophic cardiomyopathy (HCM), and is comparable to myocardial biopsy [4]. Purpose: To examine the effectiveness of CMR myocardial characterization by native T1 and T1 enhanced mapping in a heterogenous group of pediatric patients with signs concerning for cardiomyopathy or myocarditis.

Prospective evaluation of circumferential and longitudinal strain in asymptomatic children with dual ventricles who underwent single ventricle repair: comparison to single LV, single RV and normal hearts.

Background Rarely, patients with normally sized RV and LV will undergo total cavopulmonary connection (TCPC) due to the complexity of their intracardiac anatomy giving them a dual ventricle (DV) for a single cardiac output. The ventricular function in this unique physiology compared to SRV, SLV and normal hearts remains poorly understood, with few studies performed. In this study, we perform a comprehensive comparison of global and regional strain in both the circumferential (ecc) and longitudinal (eL) dimensions to conventional SV hearts and normal hearts.

Regadenoson as a pharmacologic stressor in cardiac magnetic resonance imaging in congenital and acquired pediatric heart disease: initial experience

Background Adenosine has traditionally been utilized for coronary hyperemia during myocardial perfusion assessment in adults, however regadenoson has recently become more popular [1]. With improved survival of congenital heart disease (CHD), and increased diagnosis of acquired heart disease (AHD), there’s an increasing need for assessment of myocardial perfusion in pediatrics [2]. Only dipyridamole and adenosine have reportedly been utilized as hyperemia stressors in CHD patients. As a selective A2A agonist, regadenoson has a more favorable side-effect profile and less stimulation of receptors associated with bronchospasm, and decreased chronotropy [1]. It is administered as an intravenous (IV) bolus and thus only a single IV is required. Peak onset is at 60-90 seconds, with hyperemia lasting up to 6 minutes allowing additional wall motion assessment [3].

Unsupervised free-breathing 3-dimensional imaging of morphology, function and flow in congenital heart disease under 30 minutes: pilot study

Methods Five patients with CHD were included in this pilot study (table 2 in Figure 2). The FB MR studies were performed on a Philips Acheiva 1.5T magnet using a 5-channel phased array coil (see Table 1 in Figure 1) 1. Respiratory synchronized [1], time-resolved MRA 2. Equilibrium phase MRA 3. 3D cine SSFP 4.4D phase contrast (PC) flow imaging 5.3D whole-heart single phase SSFP (coronary) Comparative data was obtained using conventional 2D cine RT SSFP sequences [2] in the VLA, 4 chamber and short axis planes, and 2D PC imaging. Data Analysis: Image quality assessment and quantitative volumetric and flow analysis were performed by three blinded, experienced users. MRA images were graded using a semi-quantitative scale from 1-5 for relevant imaging targets in CHD [1], with 1: excellent, no limitations, and 5: non-diagnostic. The clinical scoring system for 2D and 3D cine SSFP was based on bloodmyocardial contrast, endocardial edge definition and inter-slice alignment [2]. Paired t-test analysis was performed on LV and RV volumes obtained by an experienced observer using the same software

Inter -observer variability in manual measurement of aortic root dimensions in pediatric patients: benefits of using a semi-automated tool

Background Accurate measurement of maximal aortic root dimensions is important for informed decision making on the timing/ nature of aortic valve replacement surgeries in pediatric patients. Currently, the observer manually measures the following metrics to quantify maximum aortic root dimensions: 1) Cusp to Commisure (Cu-Co), and 2) Cusp to Cusp (Cu-Cu) lengths. This introduces significant interobserver variability (IOV), especially if a followup study is performed in a different institution than the previous