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Item 2023 ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Atrial Fibrillation(Elsevier, 2024) Joglar, José A.; Chung, Mina K.; Armbruster, Anastasia L.; Benjamin, Emelia J.; Chyou, Janice Y.; Cronin, Edmond M.; Deswal, Anita; Eckhardt, Lee L.; Goldberger, Zachary D.; Gopinathannair, Rakesh; Gorenek, Bulent; Hess, Paul L.; Hlatky, Mark; Hogan, Gail; Ibeh, Chinwe; Indik, Julia H.; Kido, Kazuhiko; Kusumoto, Fred; Link, Mark S.; Linta, Kathleen T.; Marcus, Gregory M.; McCarthy, Patrick M.; Patel, Nimesh; Patton, Kristen K.; Perez, Marco V.; Piccini, Jonathan P.; Russo, Andrea M.; Sanders, Prashanthan; Streur, Megan M.; Thomas, Kevin L.; Times, Sabrina; Tisdale, James E.; Valente, Anne Marie; Van Wagoner, David R.; Pharmacology and Toxicology, School of MedicineAim: The "2023 ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Patients With Atrial Fibrillation" provides recommendations to guide clinicians in the treatment of patients with atrial fibrillation. Methods: A comprehensive literature search was conducted from May 12, 2022, to November 3, 2022, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Library, the Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. Additional relevant studies, published through November 2022, during the guideline writing process, were also considered by the writing committee and added to the evidence tables, where appropriate. Structure: Atrial fibrillation is the most sustained common arrhythmia, and its incidence and prevalence are increasing in the United States and globally. Recommendations from the "2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation" and the "2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation" have been updated with new evidence to guide clinicians. In addition, new recommendations addressing atrial fibrillation and thromboembolic risk assessment, anticoagulation, left atrial appendage occlusion, atrial fibrillation catheter or surgical ablation, and risk factor modification and atrial fibrillation prevention have been developed.Item A Patch-Wise Deep Learning Approach for Myocardial Blood Flow Quantification with Robustness to Noise and Nonrigid Motion(IEEE, 2021) Youssef, Khalid; Heydari, Bobby; Rivero, Luis Zamudio; Beaulieu, Taylor; Cheema, Karandeep; Dharmakumar, Rohan; Sharif, Behzad; Medicine, School of MedicineQuantitative analysis of dynamic contrast-enhanced cardiovascular MRI (cMRI) datasets enables the assessment of myocardial blood flow (MBF) for objective evaluation of ischemic heart disease in patients with suspected coronary artery disease. State-of-the-art MBF quantification techniques use constrained deconvolution and are highly sensitive to noise and motion-induced errors, which can lead to unreliable outcomes in the setting of high-resolution MBF mapping. To overcome these limitations, recent iterative approaches incorporate spatial-smoothness constraints to tackle pixel-wise MBF mapping. However, such iterative methods require a computational time of up to 30 minutes per acquired myocardial slice, which is a major practical limitation. Furthermore, they cannot enforce robustness to residual nonrigid motion which can occur in clinical stress/rest studies of patients with arrhythmia. We present a non-iterative patch-wise deep learning approach for pixel-wise MBF quantification wherein local spatio-temporal features are learned from a large dataset of myocardial patches acquired in clinical stress/rest cMRI studies. Our approach is scanner-independent, computationally efficient, robust to noise, and has the unique feature of robustness to motion-induced errors. Numerical and experimental results obtained using real patient data demonstrate the effectiveness of our approach.Clinical Relevance- The proposed patch-wise deep learning approach significantly improves the reliability of high-resolution myocardial blood flow quantification in cMRI by improving its robustness to noise and nonrigid myocardial motion and is up to 300-fold faster than state-of-the-art iterative approaches.Item Acquired coronary-cameral fistula(Wiley, 2009-08) Jacob, Sony; Feigenbaum, Harvey; Medicine, School of MedicineItem Blood lead level in Chinese adults with and without coronary artery disease(China Science, 2021) Li, Shi-Hong; Zhang, Hong-Ju; Li, Xiao-Dong; Cui, Jian; Cheng, Yu-Tong; Wang, Qian; Wang, Su; Krittanawong, Chayakrit; El-Am, Edward A.; Bou Chaaya, Rody G.; Wu, Xiang-Yu; Gu, Wei; Liu, Hong-Hong; Yan, Xian-Liang; Li, Zhi-Zhong; Yang, Shi-Wei; Sun, Tao; Medicine, School of MedicineBackground: The Trial to Assess Chelation Therapy study found that edetate disodium (disodium ethylenediaminetetraacetic acid) chelation therapy significantly reduced the incidence of cardiac events in stable post-myocardial infarction patients, and a body of epidemiological data has shown that accumulation of biologically active metals, such as lead and cadmium, is an important risk factor for cardiovascular disease. However, limited studies have focused on the relationship between angiographically diagnosed coronary artery disease (CAD) and lead exposure. This study compared blood lead level (BLL) in Chinese patients with and without CAD. Methods: In this prospective, observational study, 450 consecutive patients admitted to Beijing Anzhen Hospital with suspected CAD from November 1, 2018, to January 30, 2019, were enrolled. All patients underwent coronary angiography, and an experienced heart team calculated the SYNTAX scores (SXscore) for all available coronary angiograms. BLLs were determined with atomic absorption spectrophotometry and compared between patients with angiographically diagnosed CAD and those without CAD. Results: In total, 343 (76%) patients had CAD, of whom 42% had low (0-22), 22% had intermediate (23-32), and 36% had high (≥ 33) SXscore. BLLs were 36.8 ± 16.95 μg/L in patients with CAD and 31.2 ± 15.75 μg/L in those without CAD (P = 0.003). When BLLs were categorized into three groups (low, middle, high), CAD prevalence increased with increasing BLLs (P < 0.05). In the multivariate regression model, BLLs were associated with CAD (odds ratio (OR): 1.023, 95% confidence interval (CI): 1.008-1.039; P = 0.0017). OR in the high versus low BLL group was 2.36 (95% CI: 1.29-4.42,P = 0.003). Furthermore, BLLs were independently associated with intermediate and high SXscore (adjusted OR: 1.050, 95% CI: 1.036-1.066; P < 0.0001). Conclusion: BLLs were significantly associated with angiographically diagnosed CAD. Furthermore, BLLs showed excellent predictive value for SXscore, especially for complex coronary artery lesions.Item Comparison of left ventriculography and coronary arteriography with positron emission tomography in assessment of myocardial viability(Wiley, 2003-02) Bourdillon, Patrick D. V.; Von Der Lohe, Elisabeth; Lewis, Stephen J.; Sharifi, Mohsen; Burt, Robert W.; Sawada, Stephen G.; Medicine, School of MedicineBackground: Assessment of viability of myocardium after an ischemic insult is an important clinical question that affects decisions pertaining to potential revascularization. The results of contrast left ventriculograms and coronary angiography were compared to positron emission tomography (PET) in 64 patients with coronary artery disease and reduced left ventricular function. Hypothesis: The study was undertaken to determine the relative utility of the invasive studies in the assessment of viability. Methods: Right anterior oblique ventriculograms were assessed for hypokinesis, akinesis, or dyskinesis in six segments. The PET scans were assessed for viability by visual estimation of flourodeoxyglucose (FDG) uptake in six segments that corresponded to the segments analyzed on the ventriculograms. Results: Of a total of 373 segments successfully analyzed by PET, 272 were judged to be viable (normal or hypokinetic) by contrast ventriculography. Of these, 253 (93%) were considered viable by PET. Of 177 segments deemed either normal or mild‐to‐moderately hypokinetic by ventriculography, 170 (94%) were viable by PET. Of 95 severely hypokinetic segments, 83 (84%) were viable by PET. Of 79 akinetic segments, 44 (56%) were considered viable by PET. For segments that were dyskinetic and thought to be nonviable by ventriculography, 19 of 22 (86%) were also considered nonviable by PET. For 294 segments for which a determination on viability was made based on the presence of wall motion on the ventriculogram (normal, hypokinetic, or dyskinetic; not akinetic), there was excellent agreement with PET (93%; p < 0.001). In 49 patients there was akinesis in no more than one segment in either the anterior or inferior territories, indicating the potential for assessment of viability by ventriculography in at least two of three segments in each territory. Coronary anatomy was analyzed to assess whether coronary patency could help in assessing viability. Segments supplied by patent arteries were more likely to be viable by PET than segments supplied by occluded arteries (p < 0.001). Akinetic segments were more likely to be supplied by occluded arteries (56 vs. 23, 72%). Dyskinetic segments were predominantly nonviable by PET (86%) and were usually supplied by occluded arteries (77%). Conclusion: In patients in whom the assessment of viability is clinically relevant, the presence of systolic inward motion on the contrast left ventriculogram correlates well with segment viability by PET, while outward or dyskinetic movement correlates well with nonviability. Thus, the use of PET to assess viability in many patients may be unnecessary.Item Coronary Artery Calcifications and Cardiac Risk after Radiotherapy for Stage III Lung Cancer(Elsevier, 2022) Wang, Kyle; Malkin, Hayley E.; Patchett, Nicholas D.; Pearlstein, Kevin A.; Heiling, Hillary M.; McCabe, Sean D.; Deal, Allison M.; Mavroidis, Panayiotis; Oakey, Mary; Fenoli, Jeffrey; Lee, Carrie B.; Klein, J. Larry; Jensen, Brian C.; Stinchcombe, Thomas E.; Marks, Lawrence B.; Weiner, Ashley A.; Biostatistics and Health Data Science, Richard M. Fairbanks School of Public HealthPurpose: Heart dose and heart disease increase the risk for cardiac toxicity associated with radiation therapy. We hypothesized that computed tomography (CT) coronary calcifications are associated with cardiac toxicity and may help ascertain baseline heart disease. Methods and materials: We analyzed the cumulative incidence of cardiac events in patients with stage III non-small cell lung cancer receiving median 74 Gy on prospective dose-escalation trials. Events were defined as symptomatic effusion, pericarditis, unstable angina, infarction, significant arrhythmia, and/or heart failure. Coronary calcifications were delineated on simulation CTs using radiation software program (130 HU threshold). Calcifications were defined as "none," "low," and "high," with median volume dividing low and high. Results: Of 109 patients, 26 had cardiac events at median 26 months (range, 1-84 months) after radiation therapy. Median follow-up in surviving patients was 8.8 years (range, 2.3-17.3). On simulation CTs, 64 patients (59%) had coronary calcifications with median volume 0.2 cm3 (range, 0.01-8.3). Only 16 patients (15%) had baseline coronary artery disease. Cardiac events occurred in 7% (3 of 45), 29% (9 of 31), and 42% (14 of 33) of patients with no, low, and high calcifications, respectively. Calcification burden was associated with cardiac toxicity on univariate (low vs none: hazard ratio [HR] 5.0, P = .015; high vs none: HR 8.1, P < .001) and multivariate analyses (low vs none: HR 7.0, P = .005, high vs none: HR 10.6, P < .001, heart mean dose: HR 1.1/Gy, P < .001). Four-year competing risk-adjusted event rates for no, low, and high calcifications were 4%, 23%, and 34%, respectively. Conclusions: The presence of coronary calcifications is a cardiac risk factor that can identify high-risk patients for medical referral and help guide clinicians before potentially cardiotoxic cancer treatments.Item Coronary Artery Disease and Aspirin Intolerance: Background and Insights on Current Management(Springer, 2022) Thakker, Ravi A.; Salazar, Leonardo; Jazar, Deaa Abu; Bhakta, Pooja; Baker, Bryan; Patel, Chandani; Elbadawi, Ayman; Agarwal, Mayank; Albaeni, Aiham; Saleh, Mohammed; Esclovan, Jonathan; El Haddad, Danielle; Alwash, Hashim; Kalra, Ankur; Goel, Sachin S.; Widmer, Robert Jay; Chatila, Khaled; Khalife, Wissam; Motiwala, Afaq; McCracken, Jennifer; Jneid, Hani; Gilani, Syed; Medicine, School of MedicineAspirin is one of the most widely used medications across the global healthcare system and is the foundation in treating ischemic heart disease, as well as secondary prevention for ischemic and valvular heart disease. Challenges arise in treating patients with cardiovascular disease who have concomitant aspirin intolerance. Through an extensive review of the literature, we provide a comprehensive background on the pharmacology of aspirin, the mechanisms behind aspirin intolerance, the importance of aspirin in cardiovascular disease, and the management of aspirin intolerance in both acute coronary syndrome and stable coronary artery disease. Our review includes a multidisciplinary approach from the internist, allergist/immunologist, and cardiologist when evaluating this important patient population.Item Coronary Smooth Muscle Cell Cytodifferentiation and Intracellular Ca2+ Handling in Coronary Artery Disease(2019-08) Badin, Jill Kimberly; Sturek, Michael S.; Evans-Molina, Carmella; Moe, Sharon; Tune, Jonathan D.Metabolic syndrome (MetS) affects 1/3 of all Americans and is the clustering of three or more of the following cardiometabolic risk factors: obesity, hypertension, dyslipidemia, glucose intolerance, and insulin resistance. MetS drastically increases the incidence of coronary artery disease (CAD), which is the leading cause of mortality globally. A cornerstone of CAD is arterial remodeling associated with coronary smooth muscle (CSM) cytodifferentiation from a contractile phenotype to proliferative and osteogenic phenotypes. This cytodifferentiation is tightly coupled to changes in intracellular Ca2+ handling that regulate several key cellular functions, including contraction, transcription, proliferation, and migration. Our group has recently elucidated the time course of Ca2+ dysregulation during MetS-induced CAD development. Ca2+ transport mechanisms, including voltage-gated calcium channels, sarcoplasmic reticulum (SR) Ca2+ store, and sarco-endoplasmic reticulum Ca2+ ATPase (SERCA), are enhanced in early, mild disease and diminished in late, severe disease in the Ossabaw miniature swine. Using this well-characterized large animal model, I tested the hypothesis that this Ca2+ dysregulation pattern occurs in multiple etiologies of CAD, including diabetes and aging. The fluorescent intracellular Ca2+ ([Ca2+]i) indicator fura-2 was utilized to measure [Ca2+]i handling in CSM from lean and diseased swine. I found that [Ca2+]i handling is enhanced in mild disease with minimal CSM phenotypic switching and diminished in severe disease with greater phenotypic switching, regardless of CAD etiology. We are confident of the translatability of this research, as the Ca2+ influx, SR Ca2+ store, and SERCA functional changes in CSM of humans with CAD are similar to those found in Ossabaw swine with MetS. Single-cell RNA sequencing revealed that CSM cells from an organ culture model of CAD exhibited many different phenotypes, indicating that phenotypic modulation is not a discreet event, but a continuum. Transcriptomic analysis revealed differential expression of many genes that are involved in the osteogenic signaling pathway and in cellular inflammatory responses across phenotypes. These genes may be another regulatory mechanism common to the different CAD etiologies. This study is the first to show that CSM Ca2+ dysregulation is common among different CAD etiologies in a clinically relevant animal model.Item Differences in Prognostic Value of Myocardial Perfusion SPECT using High-Efficiency Solid-State Detector Between Men and Women in a Large International Multi-Center Study(American Heart Association, 2022) Tamarappoo, Balaji K.; Otaki, Yuka; Sharir, Tali; Hu, Lien-Hsin; Gransar, Heidi; Einstein, Andrew J.; Fish, Mathews B.; Ruddy, Terrence D.; Kaufmann, Philipp; Sinusas, Albert J.; Miller, Edward J.; Bateman, Timothy M.; Dorbala, Sharmila; Di Carli, Marcelo; Eisenberg, Evann; Liang, Joanna X.; Dey, Damini; Berman, Daniel S.; Slomka, Piotr J.; Medicine, School of MedicineBackground: Semiquantitative assessment of stress myocardial perfusion defect has been shown to have greater prognostic value for prediction of major adverse cardiac events (MACE) in women compared with men in single-center studies with conventional single-photon emission computed tomography (SPECT) cameras. We evaluated sex-specific difference in the prognostic value of automated quantification of ischemic total perfusion defect (ITPD) and the interaction between sex and ITPD using high-efficiency SPECT cameras with solid-state detectors in an international multicenter imaging registry (REFINE SPECT [Registry of Fast Myocardial Perfusion Imaging With Next-Generation SPECT]). Methods: Rest and exercise or pharmacological stress SPECT myocardial perfusion imaging were performed in 17 833 patients from 5 centers. MACE was defined as the first occurrence of death or myocardial infarction. Total perfusion defect (TPD) at rest, stress, and ejection fraction were quantified automatically by software. ITPD was given by stressTPD-restTPD. Cox proportional hazards model was used to evaluate the association between ITPD versus MACE-free survival and expressed as a hazard ratio. Results: In 10614 men and 7219 women, with a median follow-up of 4.75 years (interquartile range, 3.7-6.1), there were 1709 MACE. In a multivariable Cox model, after adjusting for revascularization and other confounding variables, ITPD was associated with MACE (hazard ratio, 1.08 [95% CI, 1.05-1.1]; P<0.001). There was an interaction between ITPD and sex (P<0.001); predicted survival for ITPD<5% was worse among men compared to women, whereas survival among women was worse than men for ITPD≥5%, P<0.001. Conclusions: In the international, multicenter REFINE SPECT registry, moderate and severe ischemia as quantified by ITPD from high-efficiency SPECT is associated with a worse prognosis in women compared with men.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.