Person: Ghoshhajra, Brian
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Ghoshhajra
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Brian
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Ghoshhajra, Brian
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Publication Anomalous origin of the coronary artery arising from the opposite sinus: prevalence and outcomes in patients undergoing coronary CTA(Oxford University Press (OUP), 2016) Cheezum, Michael K.; Ghoshhajra, Brian; Bittencourt, Marcio S.; Hulten, Edward A.; Bhatt, Ami; Mousavi, Negareh; Shah, Nishant R.; Valente, Anne Marie; Rybicki, Frank John; Steigner, Michael; Hainer, Jon; MacGillivray, Thomas; Hoffmann, Udo; Abbara, Suhny; Di Carli, Marcelo; DeFaria Yeh, Doreen; Landzberg, Michael; Liberthson, Richard; Blankstein, RonAims The impact of coronary computed tomographic angiography (CTA) on management of anomalous origin of the coronary artery arising from the opposite sinus (ACAOS) remains uncertain. We examined the prevalence, anatomical characterization, and outcomes of ACAOS patients undergoing CTA. Methods and results Among 5991 patients referred for CTA at two tertiary hospitals between January 2004 and June 2014, we identified 103 patients (1.7% prevalence) with 110 ACAOS vessels. Mean age was 52 years (range 5–83, 63% male), with 55% previously known ACAOS and 45% discovered on CTA. ACAOS subtypes included: 39% interarterial (n = 40 anomalous right coronary artery, n = 3 anomalous left coronary artery), 38% retroaortic, 15% subpulmonic, 5% prepulmonic, and 2% other. ACAOS patients were assessed for symptoms, ischaemic test results, revascularization, all-cause or cardiovascular (CV) death, and myocardial infarction. CTAs were reviewed for ACAOS course, take-off height and angle, length and severity of proximal narrowing, intramural course, and obstructive coronary artery disease (CAD). In follow-up (median 5.8 years), there were 20 surgical revascularizations and 3 CV deaths. After adjusting for obstructive CAD (n = 21/103, 20%), variables associated with ACAOS revascularization included the following: CV symptoms, proximal vessel narrowing ≥50%, length of narrowing >5.4 mm, and an interarterial course. Conclusion The prevalence of ACAOS on CTA was 1.7%, including 45% of cases discovered incidentally. CTA provided excellent characterization of ACAOS features associated with coronary revascularization, including the length and severity of proximal vessel narrowing.Publication Perfusion decellularization of a human limb: A novel platform for composite tissue engineering and reconstructive surgery(Public Library of Science, 2018) Gerli, Mattia Francesco Maria; Guyette, Jacques Paul; Evangelista-Leite, Daniele; Ghoshhajra, Brian; Ott, HaraldMuscle and fasciocutaneous flaps taken from autologous donor sites are currently the most utilized approach for trauma repair, accounting annually for 4.5 million procedures in the US alone. However, the donor tissue size is limited and the complications related to these surgical techniques lead to morbidities, often involving the donor sites. Alternatively, recent reports indicated that extracellular matrix (ECM) scaffolds boost the regenerative potential of the injured site, as shown in a small cohort of volumetric muscle loss patients. Perfusion decellularization is a bioengineering technology that allows the generation of clinical-scale ECM scaffolds with preserved complex architecture and with an intact vascular template, from a variety of donor organs and tissues. We recently reported that this technology is amenable to generate full composite tissue scaffolds from rat and non-human primate limbs. Translating this platform to human extremities could substantially benefit soft tissue and volumetric muscle loss patients providing tissue- and species-specific grafts. In this proof-of-concept study, we show the successful generation a large-scale, acellular composite tissue scaffold from a full cadaveric human upper extremity. This construct retained its morphological architecture and perfusable vascular conduits. Histological and biochemical validation confirmed the successful removal of nuclear and cellular components, and highlighted the preservation of the native extracellular matrix components. Our results indicate that perfusion decellularization can be applied to produce human composite tissue acellular scaffolds. With its preserved structure and vascular template, these biocompatible constructs, could have significant advantages over the currently implanted matrices by means of nutrient distribution, size-scalability and immunological response.Publication An HDAC9-MALAT1-BRG1 complex mediates smooth muscle dysfunction in thoracic aortic aneurysm(Nature Publishing Group UK, 2018) Lino Cardenas, Christian; Kessinger, Chase; Cheng, Yisha; MacDonald, Carolyn; MacGillivray, Thomas; Ghoshhajra, Brian; Huleihel, Luai; Nuri, Saifar; Yeri, Ashish; Jaffer, Farouc; Kaminski, Naftali; Ellinor, Patrick; Weintraub, Neal L.; Malhotra, Rajeev; Isselbacher, Eric; Lindsay, MarkThoracic aortic aneurysm (TAA) has been associated with mutations affecting members of the TGF-β signaling pathway, or components and regulators of the vascular smooth muscle cell (VSMC) actomyosin cytoskeleton. Although both clinical groups present similar phenotypes, the existence of potential common mechanisms of pathogenesis remain obscure. Here we show that mutations affecting TGF-β signaling and VSMC cytoskeleton both lead to the formation of a ternary complex comprising the histone deacetylase HDAC9, the chromatin-remodeling enzyme BRG1, and the long noncoding RNA MALAT1. The HDAC9–MALAT1–BRG1 complex binds chromatin and represses contractile protein gene expression in association with gain of histone H3-lysine 27 trimethylation modifications. Disruption of Malat1 or Hdac9 restores contractile protein expression, improves aortic mural architecture, and inhibits experimental aneurysm growth. Thus, we highlight a shared epigenetic pathway responsible for VSMC dysfunction in both forms of TAA, with potential therapeutic implication for other known HDAC9-associated vascular diseases.Publication Salvage of diagnostic quality of image acquired by low-radiation-dose prospectively ECG-triggered coronary CTA during ventricular trigeminy: A case report of a novel image processing method(Elsevier, 2016) Vadvala, Harshna V.; Sayegh, Karl; Moy, Matthew; Staziaki, Pedro Vinícius; Ghoshhajra, BrianPublication Obesity, metabolic syndrome and cardiovascular prognosis: from the Partners coronary computed tomography angiography registry(BioMed Central, 2017) Hulten, Edward A.; Bittencourt, Marcio Sommer; Preston, Ryan; Singh, Avinainder; Romagnolli, Carla; Ghoshhajra, Brian; Shah, Ravi; Abbasi, Siddique; Abbara, Suhny; Nasir, Khurram; Blaha, Michael; Hoffmann, Udo; Di Carli, Marcelo; Blankstein, RonObjective: To investigate the relationship among body mass index (BMI), cardiometabolic risk and coronary artery disease (CAD) among patients undergoing coronary computed tomography angiography (CTA). Methods: Retrospective cohort study of 1118 patients, who underwent coronary CTA at two centers from September 2004 to October 2011. Coronary CTA were categorized as normal, nonobstructive CAD (<50%), or obstructive CAD (≥50%) in addition to segment involvement (SIS) and stenosis scores. Extensive CAD was defined as SIS > 4. Association of BMI with cardiovascular prognosis was evaluated using multivariable fractional polynomial models. Results: Mean age of the cohort was 57 ± 13 years with median follow-up of 3.2 years. Increasing BMI was associated with MetS (OR 1.28 per 1 kg/m2, p < 0.001) and burden of CAD on a univariable basis, but not after multivariable adjustment. Prognosis demonstrated a J-shaped relationship with BMI. For BMI from 20–39.9 kg/m2, after adjustment for age, gender, and smoking, MetS (HR 2.23, p = 0.009) was more strongly associated with adverse events. Conclusions: Compared to normal BMI, there was an increased burden of CAD for BMI > 25 kg/m2. Within each BMI category, metabolically unhealthy patients had greater extent of CAD, as measured by CCTA, compared to metabolically healthy patients.Publication Feasibility of aortic valve assessment with low dose prospectively triggered adaptive systolic (PTAS) cardiac computed tomography angiography(BioMed Central, 2013) Lee, Ashley M; Beaudoin, Jonathan; Wai, Bryan; Thai, Wai-Ee; Hui, Gladwin C; Sidhu, Manavjot S; Engel, Leif-Christopher; Abbara, Suhny; Hoffmann, Udo; Ghoshhajra, BrianBackground: Cardiac computed tomography angiography (CTA) is feasible for aortic valve evaluation, but retrospective gated protocols required high radiation doses for aortic valve assessment. A prospectively triggered adaptive systolic (PTAS) cardiac CT protocol was recently described in arrhythmia using second-generation dual-source CT. In this study, we sought to evaluate the feasibility of PTAS CTA to assess the aortic valve at a low radiation dose. Findings: A retrospective cohort of 29 consecutive patients whom underwent PTAS protocols for clinical indications other than aortic valve assessment and whom also received echocardiography within 2 months of CT, was identified. Images were reviewed for aortic valve morphology (tricuspid/bicuspid/prosthetic) and stenosis (AS) by experienced blinded readers. Accuracy versus echocardiography and radiation doses were assessed. All PTAS coronary CTAs were clinically diagnostic with 0 un-evaluable coronary segments. The accuracy of PTAS for aortic valve morphology was 92.6%, and for exclusion of severe AS was 93.1%. Two exams were un-evaluable for the aortic valve due to inadequate number of phases archived for interpretation. Total radiation dose was a median of 2.8 mSv (interquartile range 1.4–4.4 mSv). Conclusions: PTAS CTA protocols using second-generation dual-source CT for aortic valve evaluation are feasible at low doses. This protocol should be investigated further in larger cohorts.Publication Clinical experiences of delayed contrast enhancement with cardiac computed tomography: case series(BioMed Central, 2013) Sidhu, Manavjot S; Ghoshhajra, Brian; Uthamalingam, Shanmugam; Kilcullen, Niamh; Engel, Leif-Christopher; Medina, Hector M; Venkatesh, Vikram; Vorasettakarnkij, Yongkasem; Hoffmann, Udo; Cury, Ricardo C; Abbara, Suhny; Brady, ThomasBackground: Myocardial delayed enhancement (MDE) by gadolinium-enhanced cardiac MRI is well established for myocardial scar assessment in ischemic and non-ischemic heart disease. The role of MDE by cardiac CT (CT-MDE) is not yet defined. Findings: We reviewed all clinical cases of CT-MDE at a tertiary referral center to present the cases as a case series. All clinical cardiac CT exams which utilized CT-MDE imaging between January 1, 2005 and October 1, 2010 were collected as a series and their findings were also compared with available myocardial imaging to assess for myocardial abnormalities, including echocardiography (wall motion, morphology), cardiac MRI (delayed enhancement, morphology), SPECT MPI (perfusion defects). 5,860 clinical cardiac CT exams were performed during the study period. CT-MDE was obtained in 18 patients and was reported to be present in 9 patients. The indications for CT-MDE included ischemic and non-ischemic heart diseases. In segments positive for CT-MDE, there was excellent agreement of CT with other modalities: echocardiography (n=8) demonstrated abnormal morphology and wall motion (k=1.0 and k=0.82 respectively); prior MRI (n=2) demonstrated abnormal delayed enhancement (MR-MDE) (k=1.0); SPECT MPI (n=1) demonstrated fixed perfusion defects (k=1.0). In the subset of patients without CT-MDE, no abnormal segments were identified by echocardiography (n=8), MRI (n=1) and nuclear MPI (n=0). Conclusions: CT-MDE was performed in rare clinical situations. The indications included both ischemic and non-ischemic heart disease and there was an excellent agreement between CT-MDE and abnormal myocardium by echocardiography, cardiac MRI, and nuclear MPI.Publication Prevalence of Fat by Cardiac Magnetic Resonance Imaging Stratified by Age in 940 Patients Referred for Evaluation of Arrhythmogenic (rv) Dysplasia(BioMed Central, 2011) Medina-Zuluga, Hector; Verdini, Daniel; Deeprasertkul, Peerawut; Vorasettakarnkij, Yongkasem; Ahmed, Waleed; Neilan, Thomas; Holmvang, Gotfred; Sidhu, Manavjot Singh; Brady, Thomas; Danik, Stephan; Abbara, Suhny; Sosnovik, David; Ghoshhajra, BrianPublication The Utility of Delayed-Enhancement and T2-Weighted Cardiovascular MRI for Predicting Clinical Outcomes in Patients at High Risk for Cardiac Sarcoidosis(BioMed Central, 2011) Vorasettakarnkij, Yongkasem; Medina, Hector M; Ahmed, Waleed; Holmvang, Godtfred; Deeprasertkul, Peerawut; Verdini, Daniel J; Uthamalingam, Shanmugam; Brady, Thomas; Ghoshhajra, Brian; Sosnovik, David