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Aortic tortuosity in Turner syndrome is associated with larger ascending aorta

Srinivasan, Ranjini; Shanbhag, Sujata; Pezzini, Alessandro; Olivieri, Laura; Morris, Shaine A
Turner syndrome (TS) is associated with aortic coarctation, dissection and dilation/aneurysm. Predictors of dissection are not well delineated, making decisions regarding prophylactic root replacement challenging. In other disorders, arterial tortuosity is an imaging biomarker associated with increased risk for aortic dissection and adverse cardiovascular events. We aimed to determine if, in TS, arterial tortuosity was associated with aortic dilation or aortic events. We performed a retrospective cohort analysis of unselected women and children with TS who underwent cardiovascular magnetic resonance angiography (MRA) for a prior prospective study. We calculated tortuosity indices including vertebral artery tortuosity index, aortic arch tortuosity index, thoracic aortic tortuosity index (ATI-D), and aortic tortuosity index to the celiac artery (ATI-C). We compared tortuosity in TS patients against age and gender matched controls. We evaluated univariable and multivariable associations between the tortuosity indices and aortic root and ascending aorta size as defined by z-scores, which give a sense of how far a measurement deviates from the mean. We also studied associations between tortuosity and need for aortic root replacement or aortic dissection. Of 184 subjects, with median age 34 years, mean general aortic root z-score was 0.1 ± 1.2 and mean general ascending aortic z-score was 0.4 ± 1.5. Three patients had aortic dissection, and one had prophylactic root replacement, which all occurred prior to first MRA. Vertebral tortuosity index, ATI-D, and ATI-C all increased with age (p < 0.0001) for all. ATI-C was associated with larger general ascending z-score. In multivariable analysis, ATI-C remained independently associated with larger ascending aortic z-scores. The relationship between aortic indices and surgery/dissection could not be evaluated since all were collected post-surgery/dissection. Thoracic aortic tortuosity as measured by ATI-C is independently associated with larger ascending aortic dimensions. In this population with only three aortic dissections occurring prior to imaging assessment, we could not assess for associations between aortic tortuosity and dissection. Studies including more patients with aortic dissection are needed to draw further conclusions.
PMID: 36434337
ISSN: 1875-8312
CID: 5383362

Efficacy and Safety of COVID-19 Convalescent Plasma in Hospitalized Patients: A Randomized Clinical Trial

Ortigoza, Mila B; Yoon, Hyunah; Goldfeld, Keith S; Troxel, Andrea B; Daily, Johanna P; Wu, Yinxiang; Li, Yi; Wu, Danni; Cobb, Gia F; Baptiste, Gillian; O'Keeffe, Mary; Corpuz, Marilou O; Ostrosky-Zeichner, Luis; Amin, Amee; Zacharioudakis, Ioannis M; Jayaweera, Dushyantha T; Wu, Yanyun; Philley, Julie V; Devine, Megan S; Desruisseaux, Mahalia S; Santin, Alessandro D; Anjan, Shweta; Mathew, Reeba; Patel, Bela; Nigo, Masayuki; Upadhyay, Rabi; Kupferman, Tania; Dentino, Andrew N; Nanchal, Rahul; Merlo, Christian A; Hager, David N; Chandran, Kartik; Lai, Jonathan R; Rivera, Johanna; Bikash, Chowdhury R; Lasso, Gorka; Hilbert, Timothy P; Paroder, Monika; Asencio, Andrea A; Liu, Mengling; Petkova, Eva; Bragat, Alexander; Shaker, Reza; McPherson, David D; Sacco, Ralph L; Keller, Marla J; Grudzen, Corita R; Hochman, Judith S; Pirofski, Liise-Anne; Parameswaran, Lalitha; Corcoran, Anthony T; Rohatgi, Abhinav; Wronska, Marta W; Wu, Xinyuan; Srinivasan, Ranjini; Deng, Fang-Ming; Filardo, Thomas D; Pendse, Jay; Blaser, Simone B; Whyte, Olga; Gallagher, Jacqueline M; Thomas, Ololade E; Ramos, Danibel; Sturm-Reganato, Caroline L; Fong, Charlotte C; Daus, Ivy M; Payoen, Arianne Gisselle; Chiofolo, Joseph T; Friedman, Mark T; Wu, Ding Wen; Jacobson, Jessica L; Schneider, Jeffrey G; Sarwar, Uzma N; Wang, Henry E; Huebinger, Ryan M; Dronavalli, Goutham; Bai, Yu; Grimes, Carolyn Z; Eldin, Karen W; Umana, Virginia E; Martin, Jessica G; Heath, Timothy R; Bello, Fatimah O; Ransford, Daru Lane; Laurent-Rolle, Maudry; Shenoi, Sheela V; Akide-Ndunge, Oscar Bate; Thapa, Bipin; Peterson, Jennifer L; Knauf, Kelly; Patel, Shivani U; Cheney, Laura L; Tormey, Christopher A; Hendrickson, Jeanne E
Importance/UNASSIGNED:There is clinical equipoise for COVID-19 convalescent plasma (CCP) use in patients hospitalized with COVID-19. Objective/UNASSIGNED:To determine the safety and efficacy of CCP compared with placebo in hospitalized patients with COVID-19 receiving noninvasive supplemental oxygen. Design, Setting, and Participants/UNASSIGNED:CONTAIN COVID-19, a randomized, double-blind, placebo-controlled trial of CCP in hospitalized adults with COVID-19, was conducted at 21 US hospitals from April 17, 2020, to March 15, 2021. The trial enrolled 941 participants who were hospitalized for 3 or less days or presented 7 or less days after symptom onset and required noninvasive oxygen supplementation. Interventions/UNASSIGNED:A unit of approximately 250 mL of CCP or equivalent volume of placebo (normal saline). Main Outcomes and Measures/UNASSIGNED:The primary outcome was participant scores on the 11-point World Health Organization (WHO) Ordinal Scale for Clinical Improvement on day 14 after randomization; the secondary outcome was WHO scores determined on day 28. Subgroups were analyzed with respect to age, baseline WHO score, concomitant medications, symptom duration, CCP SARS-CoV-2 titer, baseline SARS-CoV-2 serostatus, and enrollment quarter. Outcomes were analyzed using a bayesian proportional cumulative odds model. Efficacy of CCP was defined as a cumulative adjusted odds ratio (cOR) less than 1 and a clinically meaningful effect as cOR less than 0.8. Results/UNASSIGNED:Of 941 participants randomized (473 to placebo and 468 to CCP), 556 were men (59.1%); median age was 63 years (IQR, 52-73); 373 (39.6%) were Hispanic and 132 (14.0%) were non-Hispanic Black. The cOR for the primary outcome adjusted for site, baseline risk, WHO score, age, sex, and symptom duration was 0.94 (95% credible interval [CrI], 0.75-1.18) with posterior probability (P[cOR<1] = 72%); the cOR for the secondary adjusted outcome was 0.92 (95% CrI, 0.74-1.16; P[cOR<1] = 76%). Exploratory subgroup analyses suggested heterogeneity of treatment effect: at day 28, cORs were 0.72 (95% CrI, 0.46-1.13; P[cOR<1] = 93%) for participants enrolled in April-June 2020 and 0.65 (95% CrI, 0.41 to 1.02; P[cOR<1] = 97%) for those not receiving remdesivir and not receiving corticosteroids at randomization. Median CCP SARS-CoV-2 neutralizing titer used in April to June 2020 was 1:175 (IQR, 76-379). Any adverse events (excluding transfusion reactions) were reported for 39 (8.2%) placebo recipients and 44 (9.4%) CCP recipients (P = .57). Transfusion reactions occurred in 2 (0.4) placebo recipients and 8 (1.7) CCP recipients (P = .06). Conclusions and Relevance/UNASSIGNED:In this trial, CCP did not meet the prespecified primary and secondary outcomes for CCP efficacy. However, high-titer CCP may have benefited participants early in the pandemic when remdesivir and corticosteroids were not in use. Trial Registration/ Identifier: NCT04364737.
PMID: 34901997
ISSN: 2168-6114
CID: 5084962

Right Ventricular Strain Is Associated With Increased Length of Stay After Tetralogy of Fallot Repair

Srinivasan, Ranjini; Faerber, Jennifer A; DeCost, Grace; Zhang, Xuemei; DiLorenzo, Michael; Goldmuntz, Elizabeth; Fogel, Mark; Mercer-Rosa, Laura
BACKGROUND:Little is known regarding right ventricular (RV) remodeling immediately after Tetralogy of Fallot (TOF) repair. We sought to describe myocardial deformation by cardiac magnetic resonance imaging (CMR) after TOF repair and investigate associations between these parameters and early post-operative outcomes. METHODS:Fifteen infants underwent CMR without sedation as part of a prospective pilot study after undergoing complete TOF repair, prior to hospital discharge. RV deformation (strain) was measured using tissue tracking, in addition to RV ejection fraction (EF), volumes, and pulmonary regurgitant fraction. Pearson correlation coefficients were used to determine associations between both strain and CMR measures/clinical outcomes. RESULTS:Most patients were male (11/15, 73%), with median age at TOF repair 53 days (interquartile range, 13,131). Most patients had pulmonary stenosis (vs. atresia) (11/15, 73%) and 7 (47%) received a transannular patch as part of their repair. RV function was overall preserved with mean RV EF of 62% (standard deviation [SD], 9.8). Peak radial and longitudinal strain were overall diminished (mean ± SD, 33.80 ± 18.30% and -15.50 ± 6.40%, respectively). Longer hospital length of stay after TOF repair was associated with worse RV peak radial ventricular strain (correlation coefficient (r), -0.54; p = 0.04). Greater pulmonary regurgitant fraction was associated with shorter time to peak radial RV strain (r = -0.55, p = 0.03). CONCLUSIONS:In this small study, our findings suggest presence of early decrease in RV strain after TOF repair and its association with hospital stay when changes in EF and RV size are not yet apparent.
PMID: 35086170
ISSN: 2586-7296
CID: 5154742

Strain in children with MIS-C and acute COVID-19

Minocha, Prashant K; Srinivasan, Ranjini; Babb, James; Singh, Rakesh K; Phoon, Colin K L; Better, Donna; Bhatla, Puneet
CONTEXT/UNASSIGNED:Cardiac injury has been described in both acute COVID-19 and the multisystem inflammatory syndrome in children (MIS-C). Echocardiographic strain has been shown to be a sensitive measure of systolic function. AIMS/UNASSIGNED:We sought to describe strain findings in both the groups on initial presentation and follow-up. SETTINGS AND DESIGN/UNASSIGNED:A retrospective study analyzing echocardiograms of all patients presenting with acute COVID-19 infection and MIS-C at our institution between March 2020 and December 2020 was performed. SUBJECTS AND METHODS/UNASSIGNED:TOMTEC software was used for strain analysis in both the study groups (COVID-19 and MIS-C) and age-matched healthy controls. Strain was correlated with LV ejection fraction (EF) and serum troponin levels. RESULTS/UNASSIGNED:= 0.002) and troponin in patients with MIS-C. Abnormal strain persisted in one-third of patients in the MIS-C and acute COVID-19 groups on outpatient follow-up. CONCLUSIONS/UNASSIGNED:Patients with MIS-C and acute COVID-19 can develop myocardial dysfunction as seen by abnormal strain. LV longitudinal strain correlates with cardiac injury as measured by serum troponin in patients with MIS-C. Strain may provide an additional tool in detecting subtle myocardial dysfunction. It can be routinely employed at diagnosis and at follow-up evaluation of these patients.
PMID: 37152504
ISSN: 0974-2069
CID: 5544462

Cardiac MRI identifies valvular and myocardial disease in a subset of ANO5-related muscular dystrophy patients

Srinivasan, Ranjini; Yun, Pomi; Neuhaus, Sarah; Mohassel, Payam; Dastgir, Jahannaz; Donkervoort, Sandra; Schindler, Alice; Mankodi, Ami; Foley, A Reghan; Arai, Andrew E; Bönnemann, Carsten G
Patients with bi-allelic loss-of-function mutations in the gene ANO5 most commonly present with muscular dystrophy. In some studies, patients with ANO5-related dystrophy (ANO5-RD) had evidence of mild cardiac abnormalities; however, cardiac magnetic resonance imaging (MRI) has not been used for myocardial characterization. Ten patients with genetically confirmed ANO5-RD were enrolled in a phenotyping study to better characterize cardiac involvement. Evaluations included medical history, neurological examination and cardiac evaluations (electrocardiogram, echocardiogram and cardiac MRI). All patients were clinically asymptomatic from a cardiac perspective. Muscle MRI was consistent with previous studies of ANO5-RD with increased T1 signal in the posterior and medial compartments of the upper leg and the posterior compartment of the lower leg. Cardiac studies using echocardiography and cardiac MRI revealed dilation of the aortic root and thickening of the aortic valve without significant stenosis in 3/10 patients. There was evidence of abnormal late gadolinium enhancement (LGE) on cardiac MRI in 2/10 patients. In ANO5-RD, the development of cardiac fibrosis, edema or inflammation as demonstrated by LGE has not yet been reported. Cardiac MRI can characterize cardiac tissue and may detect subtle changes before they appear on echocardiography, with potential prognostic implications.
PMID: 32819793
ISSN: 1873-2364
CID: 4778742

Successful Increase of Outpatient Clinic Continuity in a Fellowship Quality Improvement Project

Srinivasan, Ranjini; Sambatakos, Peter; Lane, Mariellen; Krishnan, Usha; Weller, Rachel; Flyer, Jonathan N; Robinson, Keith; Glickstein, Julie
Background/UNASSIGNED:Patient-to-physician continuity is the result of coordinated and consistent care. Optimizing continuity can be a challenge in medical training without impacting work hours. We sought to use quality improvement science during graduate medical training to increase outpatient continuity. Objective/UNASSIGNED:The primary goal was to improve outpatient continuity in our pediatric cardiology fellowship, without increasing trainee clinic hours, from a baseline of 38% to ≥70% within 18 months. Methods/UNASSIGNED:Our fellowship conducted a quality improvement project across 3 years to improve continuity-of-care in our outpatient clinic using the Institute for Healthcare Improvement model for improvement. We conducted Plan-Do-Study-Act cycles and completed a key driver diagram using a multidisciplinary team. We defined continuity as a patient being evaluated by their primary fellow or a different fellow that was provided a handoff. The outcome measure was the continuity rate over 2-week periods. Results/UNASSIGNED:Continuity improved from 38% to ≥80%. The improvement resulted from a series of interventions, including creating a handoff system among fellows, identifying follow-up patients in advance, and communicating this information to the clinic team. Although we anticipated a decrease when new fellows were incorporated, continuity continued to be ≥70%. This system retained continuity above 90% one year after completion of the project. Conclusions/UNASSIGNED:Our fellowship created a system change to improve primary patient-to-fellow continuity care rates. We achieved sustainable continuity by working with a multidisciplinary team without altering staffing, infrastructure, or fellow work hours. This project engaged trainees to address the practical application of quality improvement methodology to solve a common clinical problem.
PMID: 32607461
ISSN: 2472-0054
CID: 4778752

Effectiveness of dry heat application on ease of venepuncture in children with difficult intravenous access: A randomized controlled trial

Suchitra, Eva; Srinivasan, Ranjini
PURPOSE:To assess the efficacy of dry heat application in children with difficult intravenous (IV) access. DESIGN AND METHODS:A randomized controlled trial was conducted in the pediatric wards of a tertiary care hospital in a Metropolitan city in South India. Based on inclusion and exclusion criteria, children in the age group of 5-18 years were randomized into intervention and control groups of 42 children each. The intervention was an electric heating pad (40°C) applied at the site of the identified IV access for 10 min before IV insertion. Outcomes included the number of IV attempts, the time required to access the IV line, and the discomfort level of the child expressed in terms of the Oucher scale. RESULTS:(1, 84) = 18.02, p < .001. Results from regression analyses supported the unadjusted outcomes comparisons between the two groups. PRACTICE IMPLICATIONS:Dry heat application before IV line insertion significantly improves the ease of venepuncture and reduces the pain perceived by the patient. This method of IV cannulation can be adopted in children with problematic IV access.
PMID: 31600031
ISSN: 1744-6155
CID: 4895092

Multimodality Cardiac Imaging in a Patient with Kawasaki Disease and Giant Aneurysms

Srinivasan, Ranjini; Weller, Rachel; Chelliah, Anjali; Einstein, Andrew J
Kawasaki disease is a well-known cause of acquired cardiac disease in the pediatric and adult population, most prevalent in Japan but also seen commonly in the United States. In the era of intravenous immunoglobulin (IVIG) treatment, the morbidity associated with this disease has decreased, but it remains a serious illness. Here we present the case of an adolescent, initially diagnosed with Kawasaki disease as an infant, that progressed to giant aneurysm formation and calcification of the coronary arteries. We review his case and the literature, focusing on the integral role of multimodality imaging in managing Kawasaki disease.
PMID: 27872783
ISSN: 2090-6803
CID: 3984202

Erroneous glucose recordings while using mutant variant of quinoprotein glucose dehydrogenase glucometer in a child with galactosemia [Case Report]

Mathew, Vivek; Ramakrishnan, Anantharaman; Srinivasan, Ranjini; Sushma, K; Bantwal, Ganapathi; Ayyar, Vageesh
We report a 2-month-old child with galactosemia and falsely high glucose readings with a glucometer using mutant variant of quinoprotein glucose dehydrogenase (MutQ-GDH) chemistry. Potentially fatal hypoglycemia could have been induced in the child if insulin infusion had been initiated as per glycemic management protocol. Even though, the product information with the glucometer carries warning regarding interference by high galactose levels, the awareness regarding this interaction is generally poor in many practice settings. Although, false readings have been reported with glucose dehydrogenase pyrroloquinoline quinone (GDH-PQQ) glucometers, to our knowledge this is the first case report of a falsely high glucose reading due to high galactose in a proven case of galactosemia with a glucometer using the MutQ-GDH chemistry (a modified GDH-PQQ chemistry). Our experience has prompted us to write this case report and we suggest avoiding these glucometers in neonates and infants when a metabolic disease is suspected.
PMID: 24251189
ISSN: 2230-8210
CID: 3984192

A mathematical model for electrical stimulation of a monolayer of cardiac cells

Srinivasan, Ranjini; Roth, Bradley J
BACKGROUND:The goal of our study is to examine the effect of stimulating a two-dimensional sheet of myocardial cells. We assume that the stimulating electrode is located in a bath perfusing the tissue. METHODS:An equation governing the transmembrane potential, based on the continuity equation and Ohm's law, is solved numerically using a finite difference technique. RESULTS:The sheet is depolarized under the stimulating electrode and is hyperpolarized on each side of the electrode along the fiber axis. CONCLUSIONS:The results are similar to those obtained previously by Sepulveda et al. (Biophys J, 55: 987-999, 1989) for stimulation of a two-dimensional sheet of tissue with no perfusing bath present.
PMID: 14746653
ISSN: 1475-925x
CID: 3984182