Browsing by Author "Raman, Subha V."
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Item 30-minute CMR for common clinical indications: a Society for Cardiovascular Magnetic Resonance white paper(BMC, 2022-03-01) Raman, Subha V.; Markl, Michael; Patel, Amit R.; Bryant, Jennifer; Allen, Bradley D.; Plein, Sven; Seiberlich, Nicole; Medicine, School of MedicineBackground: Despite decades of accruing evidence supporting the clinical utility of cardiovascular magnetic resonance (CMR), adoption of CMR in routine cardiovascular practice remains limited in many regions of the world. Persistent use of long scan times of 60 min or more contributes to limited adoption, though techniques available on most scanners afford routine CMR examination within 30 min. Incorporating such techniques into standardize protocols can answer common clinical questions in daily practice, including those related to heart failure, cardiomyopathy, ventricular arrhythmia, ischemic heart disease, and non-ischemic myocardial injury. BODY: In this white paper, we describe CMR protocols of 30 min or shorter duration with routine techniques with or without stress perfusion, plus specific approaches in patient and scanner room preparation for efficiency. Minimum requirements for the scanner gradient system, coil hardware and pulse sequences are detailed. Recent advances such as quantitative myocardial mapping and other add-on acquisitions can be incorporated into the proposed protocols without significant extension of scan duration for most patients. Conclusion: Common questions in clinical cardiovascular practice can be answered in routine CMR protocols under 30 min; their incorporation warrants consideration to facilitate increased access to CMR worldwide.Item Cannabis Use and Heart Transplantation: Disparities and Opportunities to Improve Outcomes(American Heart Association, 2022-10-14) Ilonze, Onyedika J.; Vidot, Denise C.; Breathett, Khadijah; Camacho-Rivera, Marlene; Raman, Subha V.; Kobashigawa, Jon A.; Allen, Larry A.; Medicine, School of MedicineHeart transplantation (HT) remains the optimal therapy for many patients with advanced heart failure. Use of substances of potential abuse has historically been a contraindication to HT. Decriminalization of cannabis, increasing cannabis use, clinician biases, and lack of consensus for evaluating patients with heart failure who use cannabis all have the potential to exacerbate racial and ethnic and regional disparities in HT listing and organ allocation. Here' we review pertinent pre-HT and post-HT considerations related to cannabis use' and relative attitudes between opiates and cannabis are offered for context. We conclude with identifying unmet research needs pertaining to the use of cannabis in HT that can inform a standardized evaluation process.Item Cardiovascular Magnetic Resonance Imaging in Patients With Ibrutinib-Associated Cardiotoxicity(American Medical Association, 2023) Buck, Benjamin; Chum, Aaron P.; Patel, Mitkumar; Carter, Rebecca; Nawaz, Haseeb; Yildiz, Vedat; Ruz, Patrick; Wiczer, Tracy; Rogers, Kerry A.; Awan, Farrukh T.; Bhat, Seema; Guha, Avirup; Kittai, Adam S.; Simonetti, Orlando P.; Raman, Subha V.; Wallace, Grant; Sanchez, Reynaldo; Bonsu, Janice M.; Gambril, John; Haddad, Devin; Mann, James; Wei, Lai; Kola-Kehinde, Onaopepo; Byrd, John C.; Woyach, Jennifer A.; Addison, Daniel; Medicine, School of MedicineImportance: Ibrutinib has been associated with serious cardiotoxic arrhythmias. In preclinical models, these events are paralleled or proceeded by diffuse myocardial injury (inflammation and fibrosis). Yet whether this is seen in patients or has implications for future cardiotoxic risk is unknown. Objective: To assess the incidence and outcomes of myocardial injury among patients with ibrutinib-related cardiotoxicity. Design, setting, and participants: This cohort study included consecutive patients treated with ibrutinib from 2012 to 2019, phenotyped using cardiovascular magnetic resonance (CMR) from a large US Comprehensive Cancer Center registry. Exposures: Ibrutinib treatment for cancer control. Main outcomes and measures: The primary outcome was the presence of late gadolinium enhancement (LGE) fibrosis. The secondary outcome was the occurrence of major adverse cardiac events (MACE), defined as atrial fibrillation, heart failure, symptomatic ventricular arrhythmias, and sudden death of probable or definite ibrutinib association after CMR. We also assessed parametric-mapping subclinical fibrosis (native-T1, extracellular volume fraction) and inflammation/edema (max-T2) measures. Cardiovascular magnetic resonance measures were compared with those obtained in similar consecutive patients with cancer without ibrutinib treatment (pretreatment controls). Observed measures were also compared with similar-aged broad population rates (general-population controls) and a broader pool of cardiovascular disease (CVD) risk-matched cancer controls. Multivariable regression was used to assess the association between CMR measures and MACE. Results: Overall, 49 patients treated with ibrutinib were identified, including 33 imaged after treatment initiation (mean [SD] age, 65 [10] years, 9 [27%] with hypertension, and 23 [69.7%] with index-arrhythmias); median duration of ibrutinib-use was 14 months. The mean (SD) pretreatment native T1 was 977.0 (73.0) ms, max-T2 56.5 (4.0) ms, and 4 (13.3%) had LGE. Posttreatment initiation, mean (SD) native T1 was 1033.7 (48.2) ms, max-T2 61.5 (4.8) ms, and 17 (54.8%) had LGE (P < .001, P = .01, and P < .001, respectively, pre- vs post-ibrutinib treatment). Native T12SDs was elevated in 9 (28.6%), and max-T22SDs in 21 (63.0%), respectively. Cardiovascular magnetic resonance measures were highest in those with suspected toxic effects (P = .01 and P = .01, respectively). There was no association between traditional CVD-risk or cancer-treatment status and abnormal CMR measures. Among those without traditional CVD, 16 (58.6%) had LGE vs 38 (13.3%) in matched-controls (relative-risk, 4.8; P < .001). Over a median follow-up of 19 months, 13 (39.4%) experienced MACE. In multivariable models inclusive of traditional CVD risk factors, LGE (hazard ratio [HR], 4.9; P = .04), and native-T12SDs (HR, 3.3; P = .05) associated with higher risks of MACE. Conclusions and relevance: In this cohort study, myocardial injury was common in ibrutinib users, and its presence was associated with higher cardiotoxic risk.Item Cardiovascular magnetic resonance in women with cardiovascular disease: position statement from the Society for Cardiovascular Magnetic Resonance (SCMR)(Elsevier, 2021-05-10) Ordovas, Karen G.; Baldassarre, Lauren A.; Bucciarelli‑Ducci, Chiara; Carr, James; Fernandes, Juliano Lara; Ferreira, Vanessa M.; Frank, Luba; Mavrogeni, Sophie; Ntusi, Ntobeko; Ostenfeld, Ellen; Parwani, Purvi; Pepe, Alessia; Raman, Subha V.; Sakuma, Hajime; Schulz‑Menger, Jeanette; Sierra‑Galan, Lilia M.; Valente, Anne Marie; Srichai, Monvadi B.; Medicine, School of MedicineThis document is a position statement from the Society for Cardiovascular Magnetic Resonance (SCMR) on recommendations for clinical utilization of cardiovascular magnetic resonance (CMR) in women with cardiovascular disease. The document was prepared by the SCMR Consensus Group on CMR Imaging for Female Patients with Cardiovascular Disease and endorsed by the SCMR Publications Committee and SCMR Executive Committee. The goals of this document are to (1) guide the informed selection of cardiovascular imaging methods, (2) inform clinical decision-making, (3) educate stakeholders on the advantages of CMR in specific clinical scenarios, and (4) empower patients with clinical evidence to participate in their clinical care. The statements of clinical utility presented in the current document pertain to the following clinical scenarios: acute coronary syndrome, stable ischemic heart disease, peripartum cardiomyopathy, cancer therapy-related cardiac dysfunction, aortic syndrome and congenital heart disease in pregnancy, bicuspid aortic valve and aortopathies, systemic rheumatic diseases and collagen vascular disorders, and cardiomyopathy-causing mutations. The authors cite published evidence when available and provide expert consensus otherwise. Most of the evidence available pertains to translational studies involving subjects of both sexes. However, the authors have prioritized review of data obtained from female patients, and direct comparison of CMR between women and men. This position statement does not consider CMR accessibility or availability of local expertise, but instead highlights the optimal utilization of CMR in women with known or suspected cardiovascular disease. Finally, the ultimate goal of this position statement is to improve the health of female patients with cardiovascular disease by providing specific recommendations on the use of CMR.Item Diagnostic Costs for Ischemic Heart Disease with Treadmill Stress Cardiac Magnetic Resonance and SPECT: Results of the Multicenter, Randomized EXACT-COST Trial(Elsevier, 2020-08) Raman, Subha V.; Hachamovitch, Rory; Scandling, Debbie; Mazur, Wojciech; Kwong, Raymond Y.; Wong, Timothy C.; Schelbert, Erik B.; Moore, Sean; Truong, Vien; Simonetti, Orlando P.; Medicine, School of MedicineItem Erythrocyte Long-Chain ω-3 Fatty Acids Are Positively Associated with Lean Mass and Grip Strength in Women with Recent Diagnoses of Breast Cancer(Elsevier, 2021) Belury, Martha A.; Cole, Rachel M.; Andridge, Rebecca; Keiter, Ashleigh; Raman, Subha V.; Lustberg, Maryam B.; Kiecolt-Glaser, Janice K.; Medicine, School of MedicineBackground: Sarcopenia may hasten the risk of mortality in women with breast cancer. Long-chain omega-3 (n-3) polyunsaturated fatty acids (LCn-3PUFAs) may favor muscle mass which, in turn, could enhance resilience of cancer patients toward cancer treatment. Objectives: The objective of this study was to measure the relation of erythrocyte LCn-3PUFA concentrations with lean mass, grip strength, and postprandial energy metabolism in women with newly diagnosed breast cancer. Methods: This cross-sectional analysis evaluated women (n = 150) ages 65 y and younger who were recently diagnosed with breast cancer (stages I-III). Erythrocyte LCn-3PUFA composition was measured using GC. Body composition was measured by DXA. Grip strength was assessed at the same visit. Postprandial energy metabolism was measured for 7.5 h after the consumption of a high-calorie, high-saturated-fat test meal using indirect calorimetry. Associations of fatty acids with outcomes were analyzed using multiple linear regression models and linear mixed-effects models. Results: The ω-3 index, a measurement of LCn-3PUFA status, was positively associated with appendicular lean mass (ALM)/BMI (β = 0.015, P = 0.01) and grip strength (β = 0.757, P = 0.04) after adjusting data for age and cancer stage. However, when cardiorespiratory fitness was also included in the analyses, these relations were no longer significant (P > 0.08). After a test meal, a higher ω-3 index was associated with a less steep rise in fat oxidation (P = 0.02) and a steeper decline in glucose (P = 0.01) when adjusting for age, BMI, cancer stage, and cardiorespiratory fitness. Conclusions: The ω-3 index was positively associated with ALM/BMI and grip strength in women newly diagnosed with breast cancer and was associated with altered postprandial substrate metabolism. These findings warrant further studies to determine whether enriching the diet with LCn-3PUFAs during and after cancer treatments is causally linked with better muscle health and metabolic outcomes in breast cancer survivors.Item Evidence-based cardiovascular magnetic resonance cost-effectiveness calculator for the detection of significant coronary artery disease(BMC, 2022) Pandya, Ankur; Yu, Yuan‑Jui; Ge, Yin; Nagel, Eike; Kwong, Raymond Y.; Bakar, Rafidah Abu; Grizzard, John D.; Merkler, Alexander E.; Ntusi, Ntobeko; Petersen, Steffen E.; Rashedi, Nina; Schwitter, Juerg; Selvanayagam, Joseph B.; White, James A.; Carr, James; Raman, Subha V.; Simonetti, Orlando P.; Bucciarelli‑Ducci, Chiara; Sierra‑Galan, Lilia M.; Ferrari, Victor A.; Bhatia, Mona; Kelle, Sebastian; Medicine, School of MedicineBackground: Although prior reports have evaluated the clinical and cost impacts of cardiovascular magnetic resonance (CMR) for low-to-intermediate-risk patients with suspected significant coronary artery disease (CAD), the cost-effectiveness of CMR compared to relevant comparators remains poorly understood. We aimed to summarize the cost-effectiveness literature on CMR for CAD and create a cost-effectiveness calculator, useable worldwide, to approximate the cost-per-quality-adjusted-life-year (QALY) of CMR and relevant comparators with context-specific patient-level and system-level inputs. Methods: We searched the Tufts Cost-Effectiveness Analysis Registry and PubMed for cost-per-QALY or cost-per-life-year-saved studies of CMR to detect significant CAD. We also developed a linear regression meta-model (CMR Cost-Effectiveness Calculator) based on a larger CMR cost-effectiveness simulation model that can approximate CMR lifetime discount cost, QALY, and cost effectiveness compared to relevant comparators [such as single-photon emission computed tomography (SPECT), coronary computed tomography angiography (CCTA)] or invasive coronary angiography. Results: CMR was cost-effective for evaluation of significant CAD (either health-improving and cost saving or having a cost-per-QALY or cost-per-life-year result lower than the cost-effectiveness threshold) versus its relevant comparator in 10 out of 15 studies, with 3 studies reporting uncertain cost effectiveness, and 2 studies showing CCTA was optimal. Our cost-effectiveness calculator showed that CCTA was not cost-effective in the US compared to CMR when the most recent publications on imaging performance were included in the model. Conclusions: Based on current world-wide evidence in the literature, CMR usually represents a cost-effective option compared to relevant comparators to assess for significant CAD.Item Incidence of Major Adverse Cardiac Events at 6-Months Follow-Up in Covid-19 Positive Versus Covid-19 Negative Patients(Elsevier, 2023) Arman, Huseyin Emre; Ali, Saad; Colin, Terry; Marks, Jennifer; Raman, Subha V.; Medicine, School of MedicineBackground: The post-acute cardiovascular (CV) events due to COVID-19 is a topic of interest. We explored long-term major adverse cardiac events (MACE) related to COVID-19, defined as MI, thromboembolic events (TE), CHF, arrhythmias, and death. Methods: This is a longitudinal study of COVID-19 positive (CoVP) and negative patients (CoVN) in the first month of the pandemic with at least one follow-up encounter after 6 months. Continuous measures were summarized using means and standard deviation and compared between groups using Student's t-tests. Categorical measures were summarized using count and compared using Fisher's exact test. Results: Of 2298 patient tests between 3/6/20 and 4/5/20, 394 (50% CoVP, age 57.9±19.4, 49.2% F, and 50% CoVN, age 57.7±18.3, 49.2% F) were selected. Encounters included ED (29.7%) and inpatient (70.3%) visits. Prevalence of preexisting CV risk factors (HTN, HLD, DM, and tobacco use) were similar in CoVP and CoVN (65.5% vs 66.5%, p NS), while CHF (13.7% vs 21.8%, p 0.048), prior MI (8.6% vs 16.2%, p 0.032), and arrhythmias (15.2% vs 24.4%, p 0.031) were more prevalent in CoVN. In the cohort, 48.2% of CoVP and 60.9% of CoVN had a 6-month follow up encounter (p 0.015). The incidence of MACE in CoVP was 27.5%, whereas, in CoVN it was 42.5% (Figure 1). Conclusion: In a matched cohort of CoVP vs CoVN at the start of the pandemic, 6-month MACE was similar. False negative testing, limited access to healthcare early in the pandemic, and a high rate of comorbidities among CoVN may explain our results.Item Indexed left ventricular mass to QRS voltage ratio is associated with heart failure hospitalizations in patients with cardiac amyloidosis(Springer, 2021-03) Slivnick, Jeremy A.; Wallner, Alexander L.; Vallakati, Ajay; Truong, Vien T.; Mazur, Wojciech; Elamin, Mohamed B.; Tong, Matthew S.; Raman, Subha V.; Zareba, Karolina M.; Medicine, School of MedicineIn cardiac amyloidosis (CA), amyloid infiltration results in increased left ventricular (LV) mass disproportionate to electrocardiographic (EKG) voltage. We assessed the relationship between LV mass-voltage ratio with subsequent heart failure hospitalization (HHF) and mortality in CA. Patients with confirmed CA and comprehensive cardiovascular magnetic resonance (CMR) and EKG exams were included. CMR-derived LV mass was indexed to body surface area. EKG voltage was assessed using Sokolow, Cornell, and Limb-voltage criteria. The optimal LV mass-voltage ratio for predicting outcomes was determined using receiver operating characteristic curve analysis. The relationship between LV mass-voltage ratio and HHF was assessed using Cox proportional hazards analysis adjusting for significant covariates. A total of 85 patients (mean 69 ± 11 years, 22% female) were included, 42 with transthyretin and 43 with light chain CA. At a median of 3.4-year follow-up, 49% of patients experienced HHF and 60% had died. In unadjusted analysis, Cornell LV mass-voltage ratio was significantly associated with HHF (HR, 1.05; 95% CI 1.02-1.09, p = 0.001) and mortality (HR, 1.05; 95% CI 1.02-1.07, p = 0.001). Using ROC curve analysis, the optimal cutoff value for Cornell LV mass-voltage ratio to predict HHF was 6.7 gm/m2/mV. After adjusting for age, NYHA class, BNP, ECV, and LVEF, a Cornell LV mass-voltage ratio > 6.7 gm/m2/mV was significantly associated with HHF (HR 2.25, 95% CI 1.09-4.61; p = 0.03) but not mortality. Indexed LV mass-voltage ratio is associated with subsequent HHF and may be a useful prognostic marker in cardiac amyloidosis.Item MiR-150 attenuates maladaptive cardiac remodeling mediated by long noncoding RNA MIAT and directly represses pro-fibrotic Hoxa4(American Heart Association, 2022) Aonuma, Tatsuya; Moukette, Bruno; Kawaguchi, Satoshi; Barupala, Nipuni P.; Sepúlveda, Marisa N.; Frick, Kyle; Tang, Yaoliang; Guglin, Maya; Raman, Subha V.; Cai, Chenleng; Liangpunsakul, Suthat; Nakagawa, Shinichi; Kim, Il-man; Anatomy, Cell Biology and Physiology, School of MedicineBackground: MicroRNA-150 (miR-150) plays a protective role in heart failure (HF). Long noncoding RNA, myocardial infarction-associated transcript (MIAT) regulates miR-150 function in vitro by direct interaction. Concurrent with miR-150 downregulation, MIAT is upregulated in failing hearts, and gain-of-function single-nucleotide polymorphisms in MIAT are associated with increased risk of myocardial infarction (MI) in humans. Despite the correlative relationship between MIAT and miR-150 in HF, their in vivo functional relationship has never been established, and molecular mechanisms by which these 2 noncoding RNAs regulate cardiac protection remain elusive. Methods: We use MIAT KO (knockout), Hoxa4 (homeobox a4) KO, MIAT TG (transgenic), and miR-150 TG mice. We also develop DTG (double TG) mice overexpressing MIAT and miR-150. We then use a mouse model of MI followed by cardiac functional, structural, and mechanistic studies by echocardiography, immunohistochemistry, transcriptome profiling, Western blotting, and quantitative real-time reverse transcription-polymerase chain reaction. Moreover, we perform expression analyses in hearts from patients with HF. Lastly, we investigate cardiac fibroblast activation using primary adult human cardiac fibroblasts and in vitro assays to define the conserved MIAT/miR-150/HOXA4 axis. Results: Using novel mouse models, we demonstrate that genetic overexpression of MIAT worsens cardiac remodeling, while genetic deletion of MIAT protects hearts against MI. Importantly, miR-150 overexpression attenuates the detrimental post-MI effects caused by MIAT. Genome-wide transcriptomic analysis of MIAT null mouse hearts identifies Hoxa4 as a novel downstream target of the MIAT/miR-150 axis. Hoxa4 is upregulated in cardiac fibroblasts isolated from ischemic myocardium and subjected to hypoxia/reoxygenation. HOXA4 is also upregulated in patients with HF. Moreover, Hoxa4 deficiency in mice protects the heart from MI. Lastly, protective actions of cardiac fibroblast miR-150 are partially attributed to the direct and functional repression of profibrotic Hoxa4. Conclusions: Our findings delineate a pivotal functional interaction among MIAT, miR-150, and Hoxa4 as a novel regulatory mechanism pertinent to ischemic HF.