Publications by authors named "Sadeer G Al-Kindi"

115 Publications

Proportionate Cardiovascular Mortality in Chronic Inflammatory Disease in Adults in the United States From 1999 to 2019.

J Clin Rheumatol 2022 Jan 21. Epub 2022 Jan 21.

From the Department of Medicine, University Hospitals Harrington Heart and Vascular Institute, University Hospitals and School of Medicine, Case Western Reserve University, Cleveland, OH Department of Rheumatology, Bronson Rheumatology Specialists, Kalamazoo, MI Division of Rheumatology, Department of Medicine, University Hospitals and School of Medicine, Case Western Reserve University, Cleveland, OH.

Background: Despite a rising prevalence of chronic inflammatory disease (CID), the recent trends in cardiovascular disease (CVD) mortality of patients with CID is scarce. In this study, we investigated patterns of CVD mortality in systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), and rheumatoid arthritis (RA) compared with the general population.

Methods: We used the 1999 to 2019 multiple causes of death files from the national center for health statistics to analyze patterns and trends of proportionate CVD mortality in CID compared with the general population.

Results: We analyzed a total of 11,154 CVD deaths in IBD, 58,337 CVD deaths in RA, 6227 CVD deaths in SLE, and 17,826,871 CVD deaths in the general population. Between 1999 and 2019, we found that proportionate CVD mortality decreased significantly in the IBD group (25% to 16%), RA group (34% to 25%), and the general population (41% to 31%), but did not change for the SLE group (15% to 15%). Patients with SLE who died of CVD were approximately 10 years younger compared with CVD decedents with RA, IBD, or general population. The White population had higher proportionate CVD mortality than African American (IBD [19% vs 16%-18%] and SLE [14%-16% vs 12-14%], respectively).

Conclusions: This study identifies current trends in CVD mortality in the CID population and elucidates current demographics in CVD mortality in CID. Although proportionate CVD mortality decreased in the general population, and in patients with RA and IBD, there was no change among patients with SLE. Further studies are needed to elucidate these differences.
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http://dx.doi.org/10.1097/RHU.0000000000001818DOI Listing
January 2022

Non-Invasive Imaging in the Evaluation of Cardiac Allograft Vasculopathy in Heart Transplantation: A Systematic Review.

Curr Probl Cardiol 2022 Jan 8:101103. Epub 2022 Jan 8.

Department of Medicine, University Hospitals, Cleveland, Ohio; Harrington Heart and Vascular Institute, University Hospitals and School of Medicine, Case Western Reserve University, Cleveland, Ohio. Electronic address:

Cardiac allograft vasculopathy (CAV) is the leading cause of long-term graft dysfunction in patients with heart transplantation and is linked with significant morbidity and mortality. Currently, the gold standard for diagnosing CAV is coronary imaging with intravascular ultrasound (IVUS) during traditional invasive coronary angiography (ICA). Invasive imaging, however, carries increased procedural risk and expense to patients in addition to requiring an experienced interventionalist. With the improvements in non-invasive cardiac imaging modalities such as transthoracic echocardiography (TTE), computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET), an alternative non-invasive imaging approach for the early detection of CAV may be feasible. In this systematic review, we explored the literature to investigate the utility of non-invasive imaging in diagnosis of CAV in >3000 patients across 49 studies. We also discuss the strengths and weaknesses for each imaging modality. Overall, all four imaging modalities show good to excellent accuracy for identifying CAV with significant variations across studies. Majority of the studies compared non-invasive imaging with ICA without intravascular imaging. In summary, non-invasive imaging modalities offer an alternative approach to invasive coronary imaging for CAV. Future studies should investigate longitudinal non-invasive protocols in low-risk patients after heart transplantation.
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http://dx.doi.org/10.1016/j.cpcardiol.2022.101103DOI Listing
January 2022

Inflammatory Markers and Risk of Heart Failure With Reduced to Preserved Ejection Fraction.

Am J Cardiol 2022 Jan 2. Epub 2022 Jan 2.

Department of Medicine, School of Medicine, Case Western Reserve University, Cleveland, Ohio; Harrington Heart and Vascular Institute, University Hospitals, Cleveland, Ohio. Electronic address:

Chronic systemic inflammation is associated with an increased risk of heart failure (HF). We sought to determine the association between biomarkers of systemic inflammation interleukin (IL)-6, IL-2, tumor necrosis factor alpha (TNF-α), and C-reactive protein (CRP) with those of HF and its subtypes. We hypothesize that inflammatory biomarkers IL-6, IL-2, TNF-α, and CRP are associated with HF and its subtypes. We included participants from the Multi-Ethnic Study of Atherosclerosis (a prospective population-based cohort study [2000 to 2002]), without a history of HF, and with available baseline inflammatory biomarkers. We explored the association of IL-6, IL-2, TNF-α, and CRP with incident HF, HF with reduced ejection fraction (left ventricular ejection fraction [LVEF] <40%, HFrEF), HF with midrange EF (LVEF 40% to 50%, HFmrEF), and HF with preserved ejection fraction (LVEF >50%, HFpEF). Among 6,814 participants, 195 developed HF over 10.9 years (56 HFrEF, 30 HFmrEF, and 57 HFpEF). In the models adjusted for clinical risk factors of HF, IL-6 (hazard ratio [HR] 1.33 per doubling; 95% confidence interval [CI] 1.10 to 1.60), TNF-α (HR 2.49 per doubling; 95% CI 1.18 to 5.28), and CRP (HR 1.18 per doubling; 95% CI 1.06 to 1.30) were associated with all HF, and IL-6 (HR 1.51 per doubling; 95% CI 1.09 to 2.10) and CRP (HR 1.21 per doubling; 95% CI: 1.01 to 1.45) were associated with incident HFpEF, whereas none of the examined biomarkers were associated with HFmrEF or HFrEF. In conclusion, inflammatory biomarkers (IL-6, TNF-α, and CRP) are independently associated with incident HF. IL-6 and CRP are associated with incident HFpEF but not HFrEF or HFmrEF. These findings suggest that activation of the IL-6/CRP pathway (as cause, consequence, or epiphenomenon) may be unique to HFpEF.
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http://dx.doi.org/10.1016/j.amjcard.2021.11.045DOI Listing
January 2022

Incidence of Early Atrial Fibrillation After Transcatheter versus Surgical Aortic Valve Replacement: A Meta-Analysis of Randomized Controlled Trials.

J Atr Fibrillation 2020 Dec 31;13(4):2411. Epub 2020 Dec 31.

Harrington Heart and Vascular Institute, University Hospitals and Case Western Reserve University, Cleveland, OH.

Background: Post-operative atrial fibrillation (POAF) is common after aortic valve replacement (AVR) and is associated with worse outcomes. We performed a meta-analysis of randomized controlled trials comparing Surgical Aortic Valve Replacement (SAVR) and Transcatheter Aortic Valve Replacement (TAVR) for incidence of POAF at 30 days.

Methods: We searched databases from 1/1/1990 to 1/1/2020 for randomized studies comparing TAVR and SAVR. POAF was defined as either worsening or new-onset atrial fibrillation. Random effects model was used to estimate the risk of POAF with TAVR vs SAVR in all trials, and in subgroups (low, intermediate, high risk, and in self-expandable vs balloon expandable valves). Sensitivity analysis was performed including only studies reporting new-onset atrial fibrillation.

Results: Seven RCTs were identified that enrolled 7,934 patients (3,999 to TAVR and 3,935 to SAVR). The overall incidence of POAF was 9.7% after TAVR and 33.3% after SAVR. TAVR was associated with a lower risk of POAF compared with SAVR (OR 0.21 [0.18-0.24]; P < 0.0001). Compared with SAVR, TAVR was associated with a significantly lower risk of POAF in the high-risk cohort (OR 0.37 [0.27-0.49]; P < 0.0001), in the intermediate-risk cohort (OR 0.23 [0.19-0.28]; P < 0.0001), low-risk cohort (OR 0.13 [0.10-0.16]; P < 0.0001). Sensitivity analysis of 4 trials including only new-onset POAF showed similar summary estimates (OR 0.21, 95% CI [0.18-0.25]; P< 0.0001).

Conclusions: TAVR is associated with a significantly lower risk of post-operative atrial fibrillation compared with SAVR in all strata. Further studies are needed to identify the contribution of post-operative atrial fibrillation to the differences in clinical outcomes after TAVR and SAVR.
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http://dx.doi.org/10.4022/jafib.2411DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8691290PMC
December 2020

Myeloperoxidase is Independently Associated with Incident Heart Failure in Patients with Coronary Artery Disease and Kidney Disease.

Curr Probl Cardiol 2021 Dec 12:101080. Epub 2021 Dec 12.

Harrington Heart and Vascular Institute, University Hospitals Cleveland Medical Center and School of Medicine, Case Western Reserve University, Cleveland, OH. Electronic address:

Chronic kidney disease (CKD) is associated with high cardiovascular risk and mortality. Myeloperoxidase (MPO) has been linked to adverse events in patients with mild-moderate CKD. We sought to investigate whether MPO levels are associated with adverse outcomes in patients with CKD. We studied participants with mild to moderate CKD in the prospective chronic renal insufficiency cohort (CRIC). We followed patients for incident heart failure (HF), death, and composite outcome (myocardial infarction, incident peripheral arterial disease, cerebrovascular accident and death). A total of 3872 patients were included (2702 without CVD, 1170 with CVD). After multiple adjustments, doubling of MPO in patients with prior CAD was associated with risk of HF (HR 1.15 [1.01-1.30], P = 0.032) and mortality (HR 1.16 [1.05-1.30], P = 0.005), and composite outcome of MI, PAD, CVA and death (HR 1.12 [1.01-1.25], P = 0.031). In this cohort of patients with mild to moderate CKD and CAD, MPO levels are independently associated with incident HF, all-cause mortality, and a composite outcome.
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http://dx.doi.org/10.1016/j.cpcardiol.2021.101080DOI Listing
December 2021

Clinical and Economic Burden of Percutaneous Coronary Intervention in Hospitalized Young Adults in the United States, 2004-2018.

Curr Probl Cardiol 2021 Nov 26:101070. Epub 2021 Nov 26.

Department of Cardiology, Houston Methodist DeBakey Heart & Vascular Center, Houston, TX.

The clinical and economic burden of percutaneous coronary intervention (PCI) in young adults (18-45 years) is understudied. We used the National Inpatient Sample database between 2004 and 2018 to study trends in PCI volume, in-hospital mortality, length of stay (LOS), and health care expenditure among adults aged 18 to 44 years who underwent PCI. The data were weighted to explore national estimates of the entire US hospitalized population. We identified 558,611 PCI cases, equivalent to 31.4 per 1,000,000 person-years; 25.4% were women, and 69.5% were White adults. Overall, annual PCI volume significantly decreased from 41.6 per 100,000 in 2004 to 21.9 per 100,000 in 2018, mainly due to 83% volume reduction in non-myocardial infarction (MI) cases. The prevalence of cardiometabolic comorbidities, smoking, and drug abuse increased. Overall, in-hospital mortality was 0.87%; women had higher mortality than men (1.12% vs 0.78%; P = 0.01). The crude and risk-adjusted in-hospital mortality significantly increased between 2004 and 2018. Women, STEMI, NSTEMI, drug abuse, heart failure, peripheral vascular disease, and renal failure were associated with higher odds of in-hospital mortality. Inflation-adjusted cost significantly increased over time ($21,567 to $24,173). We noted reduction in PCI volumes but increasing mortality and clinical comorbidities among young patients undergoing PCI. Demographic disparities existed with women having higher in-hospital mortality than men.
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http://dx.doi.org/10.1016/j.cpcardiol.2021.101070DOI Listing
November 2021

Machine Learning Estimation of Low-Density Lipoprotein Cholesterol in Women with and without HIV.

J Acquir Immune Defic Syndr 2021 Nov 22. Epub 2021 Nov 22.

Department of Internal Medicine, University Hospitals/Case Western Reserve University, Cleveland, OH Division of Cardiovascular Medicine, University Hospitals/Case Western Reserve University, Cleveland, OH Department of Medicine, MetroHealth Medical Center/Case Western Reserve University, Cleveland, OH.

Introduction: Low-density lipoprotein cholesterol (LDL-C) is typically estimated from total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG). The Friedewald, Martin-Hopkins, and National Institute of Health [NIH] equations are widely used but may estimate LDL-C inaccurately in certain patient populations, such as those with HIV. We sought to investigate the utility of machine learning for LDL-C estimation in a large cohort of women with and without HIV.

Methods: We identified 7397 direct LDL-C measurements (5219 HIV, 2127 uninfected controls, 51 seroconvertors) from 2414 participants (age 39.4 ± 9.3 years) in the Women's Interagency HIV Study, and estimated LDL-C using the Friedewald, Hopkins and NIH equations. We also optimized five machine learning methods (Linear Regression, Random Forest, Gradient Boosting, Support Vector Machine and Neural Network) using 80% of the data (training set). We compared the performance of each method utilizing root mean square error (RMSE), mean absolute error (MAE) and coefficient of determination (R2) in the holdout (20%) set.

Results: Support Vector Machine (SVM) outperformed all 3 existing equations and other machine learning methods, achieving lowest RMSE, MAE and highest R2 (11.79, 7.98 mg/dL, 0.87 respectively, compared with Friedewald equation: 12.45, 9.14 mg/dL, 0.87). SVM performance remained superior in subgroups with and without HIV, with non-fasting measurements, in LDL <70 mg/dL and TG>400 mg/dL.

Conclusions: In this proof-of-concept study, SVM is a robust method that predicts directly measured LDL-C more accurately than clinically used methods in women with and without HIV. Further studies should explore the utility in broader populations.
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http://dx.doi.org/10.1097/QAI.0000000000002869DOI Listing
November 2021

Long-Term Prognostic Implications and Role of Further Testing in Adults Aged ≤55 Years With a Coronary Calcium Score of Zero (from the Multi-Ethnic Study of Atherosclerosis).

Am J Cardiol 2021 12;161:26-35

Division of Cardiovascular Prevention and Wellness, Department of Cardiology, Houston Methodist DeBakey Heart & Vascular Center, Houston, Texas; Center for Outcomes Research, Houston Methodist, Houston, Texas.

The long-term prognostic significance of a coronary artery calcium (CAC) score of 0 is poorly defined in younger adults. We evaluated this among participants aged 45 to 55 years from the Multi-Ethnic Study of Atherosclerosis, and assessed whether additional biomarkers can identify subgroups at increased absolute risk. We included 1,407 participants (61% women) without diabetes or severe hypercholesterolemia, with estimated 10-year risk <20% and CAC = 0. We evaluated all and hard cardiovascular disease (CVD) events, overall and among subjects with each of the following: high-sensitivity C-reactive protein levels ≥2 mg/L, homocysteine ≥10 µmol/L, high-sensitivity cardiac troponin T ≥95th percentile, lipoprotein (a) >50 mg/dl, triglycerides ≥175 mg/dl, apolipoprotein B ≥130 mg/dl, albuminuria, thoracic aortic calcium, aortic valve calcium (AVC), mitral annular calcium, ankle-brachial index <0.9, any carotid plaque, and maximum internal carotid artery intima-media thickness (ICA-IMT) ≥1.5 mm. Median follow-up was 16 years, and overall CVD event rates were low (4% at 15 years). For most exposures evaluated, rates of all CVD events were <6 per 1,000 person-years, except for ICA-IMT ≥1.5 mm (6.43) and AVC (13.8). The number needed to screen to detect ICA-IMT ≥1.5 mm was 8, and 84 for AVC. Among participants with borderline/intermediate risk or premature family history, hard CVD event rates were <7 per 1,000 for most exposures, except for ICA-IMT ≥1.5 mm (8.25), albuminuria (8.30), and AVC (13.47). Nonsmokers and those with ICA-IMT <1.5 mm had very low rates. In conclusion, our results demonstrate a favorable long-term prognosis of CAC = 0 among adults aged ≤55 years, particularly among nonsmokers. ICA-IMT testing could be considered for further risk assessment in adults ≤55 years with CAC = 0 and uncertain management.
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http://dx.doi.org/10.1016/j.amjcard.2021.08.067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8607758PMC
December 2021

Social Vulnerability and Premature Cardiovascular Mortality Among US Counties, 2014 to 2018.

Circulation 2021 10 18;144(16):1272-1279. Epub 2021 Oct 18.

Cardiovascular Prevention and Wellness (M.C-A., K.N.), DeBakey Heart and Vascular Center.

Background: Substantial differences exist between United States counties with regards to premature (<65 years of age) cardiovascular disease (CVD) mortality. Whether underlying social vulnerabilities of counties influence premature CVD mortality is uncertain.

Methods: In this cross-sectional study (2014-2018), we linked county-level CDC/ATSDR SVI (Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry Social Vulnerability Index) data with county-level CDC WONDER (Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiological Research) mortality data. We calculated scores for overall SVI and its 4 subcomponents (ie, socioeconomic status; household composition and disability; minority status and language; and housing type and transportation) using 15 social attributes. Scores were presented as percentile rankings by county, further classified as quartiles on the basis of their distribution among all US counties (1st [least vulnerable] = 0 to 0.25; 4th [most vulnerable = 0.75 to 1.00]). We grouped age-adjusted mortality rates per 100 000 person-years for overall CVD and its subtypes (ischemic heart disease, stroke, hypertension, and heart failure) for nonelderly (<65 years of age) adults across SVI quartiles.

Results: Overall, the age-adjusted CVD mortality rate per 100 000 person-years was 47.0 (ischemic heart disease, 28.3; stroke, 7.9; hypertension, 8.4; and heart failure, 2.4). The largest concentration of counties with more social vulnerabilities and CVD mortality were clustered across the southwestern and southeastern parts of the United States. The age-adjusted CVD mortality rates increased in a stepwise manner from 1st to 4th SVI quartiles. Counties in the 4th SVI quartile had significantly higher mortality for CVD (rate ratio, 1.84 [95% CI, 1.43-2.36]), ischemic heart disease (1.52 [1.09-2.13]), stroke (2.03 [1.12-3.70]), hypertension (2.71 [1.54-4.75]), and heart failure (3.38 [1.32-8.61]) than those in the 1st SVI quartile. The relative risks varied considerably by demographic characteristics. For example, among all ethnicities/races, non-Hispanic Black adults in the 4th SVI quartile versus the 1st SVI quartile exclusively had significantly higher relative risks of stroke (1.65 [1.07-2.54]) and heart failure (2.42 [1.29-4.55]) mortality. Rural counties with more social vulnerabilities had 2- to 5-fold higher mortality attributable to CVD and subtypes.

Conclusions: In this analysis, US counties with more social vulnerabilities had higher premature CVD mortality, varied by demographic characteristics and rurality. Focused public health interventions should address the socioeconomic disparities faced by underserved communities to curb the growing burden of premature CVD.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.121.054516DOI Listing
October 2021

Trends in Characteristics and Outcomes of Hospitalized Young Patients Undergoing Coronary Artery Bypass Grafting in the United States, 2004 to 2018.

J Am Heart Assoc 2021 09 28;10(17):e021361. Epub 2021 Aug 28.

Department of Cardiology Houston Methodist DeBakey Heart & Vascular Center Houston TX.

Background Data are limited about young adults' characteristics and outcomes undergoing coronary artery bypass grafting (CABG). Methods and Results We used the National Inpatient Sample database to identify adults aged 18 to 45 years who underwent CABG between 2004 and 2018. The data were weighted to generate national estimates of the entire US hospitalized population. We identified 110 463 CABG cases, equivalent to 62.2 per 1 000 000 person-years; 27.1% were women, and 70.2% were White adults. Overall, annual CABG volume per 1 000 000 significantly decreased from 87.3 in 2004 to 45.7 in 2018. The prevalence of obesity, diabetes mellitus, hypertension, drug abuse, and chronic medical conditions increased over time. Overall, inpatient mortality was 1.76%; ST-segment-elevation myocardial infarction, non-ST-segment-elevation myocardial infarction, heart failure, peripheral vascular disease, renal failure, and valvular surgery were associated with higher inpatient mortality. Women had higher inpatient mortality than men (2.29% versus 1.57%), and Black patients had higher deaths than White patients (2.86% versus 1.58%). Inpatient mortality remained stable overall, according to sex, race, or clinical indication of CABG. However, the mean length of stay (8.4 days in 2004 to 9.5 days in 2018) and inflation-adjusted cost of care ($40 522.8 in 2004 to $52 434.2 in 2018) significantly increased during the study period. Conclusions Despite the increased burden of cardiometabolic risk factors, the inpatient mortality in young adults undergoing CABG remained stable during the last 15 years. However, CABG volumes have decreased, but length of stay and inflation-adjusted costs have increased over time.
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http://dx.doi.org/10.1161/JAHA.121.021361DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8649273PMC
September 2021

Ambient Air Pollution and Atherosclerosis: Recent Updates.

Curr Atheroscler Rep 2021 08 21;23(10):63. Epub 2021 Aug 21.

Department of Medicine, University Hospitals Cleveland Medical Center, Cleveland, OH, USA.

Purpose Of Review: During the past century, exposure to particulate matter (PM) air pollution < 2.5 μm in diameter (PM) has emerged as an all-pervading element of modern-day society. This increased exposure has come at the cost of heightened risk for cardiovascular (CV) morbidity and mortality. Not only can short-term PM exposure trigger acute CV events in susceptible individuals, but longer-term exposure over years augments CV risk to a greater extent in comparison with short-term exposure. The purpose of this review is to examine the available evidence for how ambient air pollution exposure may precipitate events at various time frames.

Recent Findings: Recent epidemiological studies have demonstrated an association between ambient PM exposure and the presence and progression of atherosclerosis in humans. Multiple animal exposure experiments over two decades have provided strong corroborative evidence that chronic exposure in fact does enhance the progression and perhaps vulnerability characteristics of atherosclerotic lesions. Evidence from epidemiological studies including surrogates of atherosclerosis, human translational studies, and mechanistic investigations utilizing animal studies have improved our understanding of how ambient air pollution may potentiate atherosclerosis and precipitate cardiovascular events. Even so, future research is needed to fully understand the contribution of different constituents in ambient air pollution-mediated atherosclerosis as well as how other systems may modulate the impact of exposure including adaptive immunity and the gut microbiome. Nevertheless, due to the billions of people continually exposed to PM, the long-term pro-atherosclerotic effects of this ubiquitous air pollutant are likely to be of enormous and growing global public health importance.
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http://dx.doi.org/10.1007/s11883-021-00958-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8379601PMC
August 2021

Outcomes of cardiac diffuse large B-cell lymphoma (DLBCL) in the rituximab era.

Int J Cardiol 2021 Sep 26;339:146-149. Epub 2021 Jul 26.

Harrington Heart and Vascular Institute, University Hospitals, Cleveland, OH, United States of America; School of Medicine, Case Western Reserve University, Cleveland, OH, United States of America. Electronic address:

Background Cardiac diffuse large B-cell lymphoma (cDLBCL) is an extremely rare disease. Introduction of rituximab has significantly improved survival in non-cardiac DLBCL, but there is limited data regarding the effects on outcomes in cDLBCL. We sought to evaluate the outcomes of cDLBCL in both pre- and rituximab eras. Methods We identified all cDLBCL cases in the Surveillance, Epidemiology and End Results (SEER) registry from 1975 to 2016. We compared survival (overall and lymphoma-specific) of patients diagnosed prior to versus after rituximab approval in 2006. Results A total of 106 patients were included in the final analysis. Median age was 69.5 years, 67% of the patients were white and 64% had local stage I/II disease. 67% of the patients were diagnosed after 2006 and thus belonged to the rituximab era group. Overall, 77% received chemotherapy, 24% had surgery and 15% had radiotherapy. Median overall survival (OS) for the entire cohort was 22 months. Median OS was 16 months (95% CI, 0.55-31) for the pre-rituximab group, versus 26 months (95% CI, 7.5-45) for the rituximab group (p = 0.34). Median lymphoma-specific survival (LSS) was 30 months (95% CI, 8.0-52) for the pre-rituximab group versus 36 months (95% CI, 16-158) for the rituximab group (p = 0.30). OS and LSS were also not significantly different between the two era groups when stratified by chemotherapy. In multivariable analysis, both OS and LSS were associated with lymphoma stage, insurance status and age but not with diagnosis era or chemotherapy. Conclusions Cardiac DLBCLs are rare and affecting mostly the elderly. Younger age, limited disease stage, and having health insurance but not lymphoma diagnosis era were associated with better outcomes.
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http://dx.doi.org/10.1016/j.ijcard.2021.07.043DOI Listing
September 2021

LVAD Vasculitis Case Series: Suggestion of a New Fatal LVAD-Related Phenomenon.

JACC Case Rep 2021 Jul 7;3(7):1013-1017. Epub 2021 Jul 7.

Department of Advanced Heart Failure and Transplant, University Hospital Cleveland Medical Center, Harrington Heart Vascular Institute, Case Western Reserve University, Cleveland, Ohio, USA.

Left ventricular assist devices (LVADs) are surgically implanted mechanical devices indicated for patients with advanced heart failure and are known to come with several complications. Here we present a case series, and review 1 documented report, of LVAD vasculitis, a presumed new LVAD immune/humoral related phenomenon. ().
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http://dx.doi.org/10.1016/j.jaccas.2021.03.030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8311371PMC
July 2021

Anisocytosis Is Associated With Reduced Bone Marrow Activity Evaluated by Positron Emission Tomography.

Am J Cardiol 2021 08 11;152:179-180. Epub 2021 Jun 11.

Department of Medicine and Pediatrics, University Hospital Cleveland Medical Center, Cleveland, Ohio; School of Medicine, Case Western Reserve University, Cleveland, Ohio. Electronic address:

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http://dx.doi.org/10.1016/j.amjcard.2021.05.001DOI Listing
August 2021

Benign Metastasizing Leiomyoma in the Heart of a 45-Year-Old Woman.

Tex Heart Inst J 2021 01;48(1)

Harrington Heart & Vascular Institute, Cardiovascular Medicine Department, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, Cleveland, Ohio.

We report a rare case of benign metastasizing leiomyoma in the heart of a 45-year-old woman 2 years after a uterine leiomyoma had been discovered during hysterectomy. Computed tomograms at presentation showed a large mixed cystic mass in the pelvis and bilateral lung nodules suggestive of metastatic disease. A large cardiac mass, attached to the chordae of the tricuspid valve and later shown to be histopathologically consistent with uterine leiomyoma, was successfully resected through a right atriotomy. This case suggests that benign metastasizing leiomyoma should be considered in the differential diagnosis of right-sided cardiac tumors.
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http://dx.doi.org/10.14503/THIJ-19-7066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8108713PMC
January 2021

Myocardial Injury and the Risk of Stroke in Patients With Chronic Kidney Disease (From the Chronic Renal Insufficiency Cohort Study).

Angiology 2021 Apr 7:33197211005595. Epub 2021 Apr 7.

Harrington Heart and Vascular Institute, 24575University Hospitals Cleveland Medical Center, OH, USA.

Patients with chronic kidney disease (CKD) are at increased risk for stroke. High-sensitivity troponin (hsTP), a marker of myocardial injury, has been associated with stroke risk in patients without CKD, but whether this applies to patients with CKD is not known. We assessed whether hsTP levels is associated with incident stroke in patients with mild-to-moderate CKD without a history of stroke enrolled in the Chronic Renal Insufficiency Cohort. Patients were followed for incident stroke, and the association with hsTP was assessed. A total of 3477 patients without prior stroke were included in this investigation. Over a median follow-up of 7.3 years, 101 (2.8%) patients had an incident stroke. Baseline hsTP was associated with a 9-year risk of stroke (quartile 1: 1.8%, quartile 2: 3.8%, quartile 3: 4.9%, quartile 4: 7.3%; < .001). After adjusting for traditional stroke risk factors, patients in the fourth quartile (hazard ratio: 2.52, 95% CI: 1.10-5.76, = .021) had higher risk of stroke when compared with the lowest quartile of hsTP. In conclusion, hsTP levels are associated with increased risk of incident stroke in patients with mild to moderate CKD, and this association remains significant despite the adjustment for traditional risk factors and CKD.
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http://dx.doi.org/10.1177/00033197211005595DOI Listing
April 2021

Outcomes of Durable Mechanical Circulatory Support in Myocarditis: Analysis of the International Society for Heart and Lung Transplantation Registry for Mechanically Assisted Circulatory Support Registry.

ASAIO J 2021 Mar 22. Epub 2021 Mar 22.

From the Harrington Heart and Vascular Institute, University Hospitals Cleveland Medical Center, Cleveland, Ohio Department of Surgery, The University of Alabama at Birmingham, Birmingham, Alabama Department of Cardiology, Advanced Heart Failure and Transplant Cardiology, Henry Ford Health System, Detroit, Michigan Division of Cardiovascular Sciences, University of South Florida, Tampa, Florida Deutsches Herzzentrum Berlin, Berlin, Germany Department of Transplantation, National Cerebral and Cardiovascular Center, Osaka, Japan Department of Cardiothoracic & Vascular Surgery, Newcastle/Freeman Hospital, UK, Newcastle, United Kingdom Alfred Heart Center, Melbourne, Victoria, Australia Department of Cardiovascular Surgery, Montefiore Medical Center, Bronx, New York.

Myocarditis can be refractory to medical therapy and require durable mechanical circulatory support (MCS). The characteristics and outcomes of these patients are not known. We identified all patients with clinically-diagnosed or pathology-proven myocarditis who underwent mechanical circulatory support in the International Society for Heart and Lung Transplantation Registry for Mechanically Assisted Circulatory Support registry (2013-2016). The characteristics and outcomes of these patients were compared to those of patients with nonischemic cardiomyopathy (NICM). Out of 14,062 patients in the registry, 180 (1.2%) had myocarditis and 6,602 (46.9%) had NICM. Among patients with myocarditis, duration of heart failure was <1 month in 22%, 1-12 months in 22.6%, and >1 year in 55.4%. Compared with NICM, patients with myocarditis were younger (45 vs. 52 years, P < 0.001) and were more often implanted with Interagency Registry for Mechanically Assisted Circulatory Support profile 1 (30% vs. 15%, P < 0.001). Biventricular mechanical support ( biventricular ventricular assist device [BIVAD] or total artificial heart) was implanted more frequently in myocarditis (18% vs. 6.7%, P < 0.001). Overall postimplant survival was not different between myocarditis and NICM (left ventricular assist device: P = 0.27, BIVAD: P = 0.50). The proportion of myocarditis patients that have recovered by 12 months postimplant was significantly higher in myocarditis compared to that of NICM (5% vs. 1.7%, P = 0.0003). Adverse events (bleeding, infection, and neurologic dysfunction) were all lower in the myocarditis than NICM. In conclusion, although myocarditis patients who receive durable MCS are sicker preoperatively with higher needs for biventricular MCS, their overall MCS survival is noninferior to NICM. Patients who received MCS for myocarditis are more likely than NICM to have MCS explanted due to recovery, however, the absolute rates of recovery were low.
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http://dx.doi.org/10.1097/MAT.0000000000001430DOI Listing
March 2021

Cystic left ventricular mass: the utility of transthoracic echocardiography and cardiac MRI.

BMJ Case Rep 2021 Feb 26;14(2). Epub 2021 Feb 26.

Harrington Heart and Vascular Institute, University Hospitals Case Medical Center, Cleveland, Ohio, USA.

Accurate identification of left ventricular masses (LVM) can be challenging, and if incorrect, may have devastating consequences. While transthoracic echocardiography is often the first test to identify intracardiac masses, cardiac MRI (CMRI) allows for better anatomical definition and tissue characterisation. We present a case of a 51-year-old man who presented with 4 weeks of shortness of breath, found on echocardiogram to have severely reduced LV function and a 2.5×4.0 cm LVM with a hypolucent/cystic core. Due to the unusual appearance, CMRI was required for confirmation of an LV thrombus. This case highlights the importance of multimodality imaging in the discovery and identification of LVM.
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http://dx.doi.org/10.1136/bcr-2020-239985DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919553PMC
February 2021

Endothelin-1 and peak oxygen consumption in patients with heart failure with preserved ejection fraction.

Heart Lung 2021 May-Jun;50(3):442-446. Epub 2021 Feb 23.

Harrington Heart and Vascular Institute, University Hospitals Cleveland Medical Center and School of Medicine, Case Western Reserve University, Cleveland, OH, USA. Electronic address:

Background: Mechanisms of exercise intolerance in patients with heart failure with preserved ejection fraction (HFpEF) are not well understood. Pulmonary hypertension, a common accompaniment in patients with HFpEF, is associated with poor outcomes. While Endothelin -1 (ET-1) plays a mechanistic role in pulmonary hypertension, its role in exercise intolerance in HFpEF is not well established.

Objective: To explore the association between plasma ET-1 levels and maximal oxygen consumption (pVO2), and their changes over 24 weeks in HFpEF.

Methods: This is a post-hoc analysis of the Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Heart Failure with Preserved Ejection Fraction (RELAX) trial. We performed linear regressions to assess the relationship between plasma ET-1 and pVO2. We also used linear regressions to determine whether ET-1 was associated with change in peak VO2 (ΔpVO).

Results: A total of 210 patients were included. Baseline plasma ET-1 levels were associated with older age, higher NT-proBNP levels, higher serum creatinine levels, and higher prevalence of atrial fibrillation. Patients with higher ET1 levels also had higher plasma galectin-3 and CITP levels. After multiple adjustments, baseline ET1 levels were associated with lower pVO (β -0.927, SE 0.196, p < 0.001). Over 24 weeks, the change in ET1 levels was associated with the change in pVO2 (multivariable adjusted β -0.415, SE 0.115, p = 0.018). Baseline ET1 levels did not modify the effect of sildenafil on change in peak VO.

Conclusions: Plasma ET1 levels are significantly associated with lower exercise oxygen consumption both at baseline and longitudinally over 24 weeks. Future studies should explore Endothelin-1 antagonism to improve exercise tolerance in HFpEF.
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http://dx.doi.org/10.1016/j.hrtlng.2021.02.004DOI Listing
April 2021

Association between ambient air pollution and county-level cardiovascular mortality in the United States by social deprivation index.

Am Heart J 2021 05 13;235:125-131. Epub 2021 Feb 13.

School of Medicine, Case Western Reserve University, Cleveland, OH; Harrington Heart and Vascular Institute, University Hospitals, Cleveland, OH. Electronic address:

Background: Air pollution and socioeconomic status have both been strongly associated with cardiovascular (CV) outcomes. We sought to determine if socioeconomic status modifies the risk association between fine particulate matter air pollution (PM) and CV mortality.

Methods: We linked county-level age-adjusted CV mortality data from Multiple Cause of Death files (2000-2016, ICD10: I00-I99) with 2015 Social Deprivation Index (SDI), a validated estimate of socioeconomic status, and modelled spatial and temporal mean annual PM exposures (2012-2018). Higher SDI suggests greater deprivation and lower socioeconomic status. Associations between PM and age adjusted CV mortality were estimated using linear models.

Results: A total of 5,769,315 cardiovascular deaths from 2012-2018 across 3106 United States counties were analyzed. Both PM (β (SE) 7.584 (0.938), P < .001) and SDI scores (β (SE) 0.591 (0.140), P < .001) were independently associated with age-adjusted CV mortality (R = 0.341). The association between PM and CV mortality were stronger among counties with highest SDI, P value for interaction = .012.

Conclusion: Social deprivation and PM exposures were independently associated with county level age-adjusted CV mortality. The associations between PM and CV mortality were stronger in counties with high vs low social deprivation. SDI and PM represent potential targets to reduce CV mortality disparities and interventions to reduce PM exposure may be most impactful in communities of low socioeconomic status.
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http://dx.doi.org/10.1016/j.ahj.2021.02.005DOI Listing
May 2021

The Benefits of Intensive Versus Standard Blood Pressure Treatment According to Fine Particulate Matter Air Pollution Exposure: A Post Hoc Analysis of SPRINT.

Hypertension 2021 03 1;77(3):813-822. Epub 2021 Feb 1.

From the Department of Medicine, University Hospitals Cleveland Medical Center, Case Western Reserve University, OH (S.G.A.-K., J.T.W., S.R.).

Fine particulate matter <2.5 µm (PM) air pollution is implicated in global mortality, especially from cardiovascular causes. A large body of evidence suggests a link between PM and elevation in blood pressure (BP), with the latter implicated as a potential mediator of cardiovascular events. We sought to determine if the outcomes of intensive BP lowering (systolic BP <120 mm Hg) on cardiovascular events are modified by PM exposure in the SPRINT (Systolic BP Intervention Trial). We linked annual PM exposure estimates derived from an integrated model to subjects participating in SPRINT. We evaluated the effect of intensive BP lowering by PM exposure on the primary outcome in SPRINT using cox-proportional hazard models. A total of 9286 participants were linked to PM levels (mean age 68±9 years). Intensive BP-lowering decreased risk of the primary outcome more among patients exposed to higher PM (=0.047). The estimate for lowering of primary outcome was numerically lower in the highest than in the lower quintiles. The benefits of intensive BP-lowering were larger among patients chronically exposed to PM levels above US National Ambient Air Quality Standards of 12 µg/m (hazard ratio, 0.47 [95% CI, 0.29-0.74]) compared with those living in cleaner locations (hazard ratio, 0.81 [95% CI, 0.68-0.97]), =0.037. This exploratory nonprespecified post hoc analysis of SPRINT suggests that the benefits of intensive BP lowering on the primary outcome was greater in patients exposed to higher PM, suggesting that the magnitude of benefit may depend upon the magnitude of antecedent PM exposure.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.15923DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8485988PMC
March 2021

Performance of Methods to Estimate Low-Density Lipoprotein Cholesterol in Women With and Without HIV Infection.

J Acquir Immune Defic Syndr 2021 05;87(1):750-754

Division of Cardiovascular Medicine, University Hospitals/Case Western Reserve University, Cleveland, OH.

Background: Low-density lipoprotein cholesterol (LDL-C) is estimated from total cholesterol, high-density lipoprotein cholesterol and triglycerides using predefined equations which assume fixed or varying relationships between these parameters and may underestimate or overestimate LDL-C. Data on the performance of these equations in persons with HIV are limited. We sought to investigate the utility of the 3 most widely used methods (Friedewald, Hopkins, and the recently proposed NIH equation) to predict LDL-C in persons with HIV.

Methods: We identified 7397 direct LDL-C (5219 HIV, 2127 uninfected controls, 51 seroconvertors) measurements in the Women's Interagency HIV Study, and used the 3 equations (Friedewald, Hopkins, and NIH) to calculate LDL-C. We compared the performance of the 3 equations using root mean square error and coefficient of determination (R2).

Results: Overall, the Friedewald equation had the best performance characteristics, outperforming Hopkins and NIH methods with lower root mean square error and higher R2 at lower triglyceride levels. However, this association did not hold true at higher triglyceride levels (quartiles 3 and 4), whereas the Hopkins equation had better performance characteristics in quartile 3, none of the 3 equations were optimal in quartile 4. After adjusting for fasting status and triglycerides levels, HIV+ had larger mean difference compared with directly measured LDL using all 3 methods.

Conclusions: All 3 methods have lower accuracy in HIV+ vs HIV- women, even after adjusting for triglyceride levels and fasting status. Further research should focus on identifying methods to estimate LDL-C in HIV.
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http://dx.doi.org/10.1097/QAI.0000000000002631DOI Listing
May 2021

Ambient Air Pollution and Atherosclerosis: Insights Into Dose, Time, and Mechanisms.

Arterioscler Thromb Vasc Biol 2021 02 17;41(2):628-637. Epub 2020 Dec 17.

Harrington Heart and Vascular Institute, University Hospitals Cleveland Medical Center and School of Medicine, OH (G.H.B., S.G.A.-K., S.R.).

Ambient air pollution due to particulate matter ≤2.5 μ is the leading environmental risk factor contributing to global mortality, with a preponderant majority of these deaths attributable to atherosclerotic cardiovascular disease (ASCVD) causes such as stroke and myocardial infarction. Epidemiological studies in humans have provided refined estimates of exposure risk, with evidence suggesting that risk association with particulate matter ≤2.5 levels and ASCVD continues at levels well below air quality guidelines in North America and Europe. Mechanistic studies in animals and humans have provided a framework of understanding of the duration and pathways by which air pollution exposure may predispose to atherosclerosis. Although acute exposure to particulate matter ≤2.5 is associated with oxidative stress and inflammation, system transmission of signals from the lungs to extrapulmonary sites may involve direct translocation of components, biologic intermediates, and autonomic nervous system activation. End-organ effector pathways such as endothelial barrier disruption/dysfunction, thrombosis, vasoconstriction/increased blood pressure, and plaque instability, may contribute to ASCVD. The strength of the association of air pollution with ASCVD offers an opportunity to mitigate its consequences. Although elimination of anthropogenic sources of air pollution with a switch to clean energy provides the ultimate solution, this may not be possible in the interim and may require personal protection efforts and an integrated approach to managing risk posed by air pollution for ASCVD.
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http://dx.doi.org/10.1161/ATVBAHA.120.315219DOI Listing
February 2021

Cardiovascular risk assessment and management of patients undergoing hematopoietic cell transplantation.

Bone Marrow Transplant 2021 03 31;56(3):544-551. Epub 2020 Oct 31.

Department of Medicine, Case Western Reserve University, Cleveland, OH, USA.

The purpose of this review is to provide a framework for the cardiovascular evaluation and management of patients undergoing hematopoietic cell transplantation (HCT). To accomplish this, we have performed an extensive literature review, critically analyzed the available evidence, and developed a set of recommendations to guide best practice. Herein, we discuss the cardiovascular risk profile of patients undergoing HCT along with putative mechanisms of HCT-induced cardiovascular injury. We then present an algorithm for cardiovascular testing and risk mitigation of potential recipients. Last, we address the management of the most prevalent cardiovascular conditions associated with HCT recipients.
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http://dx.doi.org/10.1038/s41409-020-01080-1DOI Listing
March 2021

Anisocytosis is Associated With Short-Term Mortality in COVID-19 and May Reflect Proinflammatory Signature in Uninfected Ambulatory Adults.

Pathog Immun 2020 2;5(1):312-326. Epub 2020 Oct 2.

Harrington Heart & Vascular Institute, University Hospitals Cleveland Medical Center.

Background: Red cell distribution width (RDW), a measure of anisocytosis, is observed in chronic inflammation and is a prognostic marker in critically ill patients without COVID-19, but data in COVID-19 are limited.

Methods: Between March 12 and April 19, 2020, 282 individuals with confirmed COVID-19 and RDW available within 7 days prior to COVID-19 confirmation were evaluated. Individuals were grouped by quartiles of RDW. Association between quartiles of RDW and mortality was assessed using the Kaplan-Meier method and statistical significance was assessed using the log-rank test. The association between RDW and all-cause mortality was further assessed using a Cox proportional hazards model. Plasma cytokine levels in uninfected ambulatory adults without cardiovascular disease (n=38) were measured and bivariate Spearman correlations and principle components analysis were used to identify relationships between cytokine concentrations with RDW.

Results: After adjusting for age, sex, race, cardiovascular disease, and hemoglobin, there was an association between RDW and mortality (Quartile 4 vs Quartile 1: HR 4.04 [1.08-15.07]), with each 1% increment in RDW associated with a 39% increased rate of mortality (HR 1.39 [1.21-1.59]). Remote RDW was also associated with mortality after COVID-19 infection. Among uninfected ambulatory adults without cardiovascular disease, RDW was associated with elevated pro-inflammatory cytokines (TNF-α, IL8, IL6, IL1b), but not regulatory cytokines (TGFb).

Conclusions: Anisocytosis predicts short-term mortality in COVID-19 patients, often predates viral exposure, and may be related to a pro-inflammatory phenotype. Additional study of whether the RDW can assist in the early identification of pending cytokine storm is warranted.
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http://dx.doi.org/10.20411/pai.v5i1.391DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7556412PMC
October 2020

Prevalence and manifestations of diagnosed fibromuscular dysplasia by sex and race: Analysis of >4500 FMD cases in the United States.

Heart Lung 2021 Jan - Feb;50(1):168-173. Epub 2020 Oct 15.

Department of Medicine, University Hospitals, Cleveland, OH USA; School of Medicine, Case Western Reserve University, Cleveland, OH USA; Harrington Heart and Vascular Institute, University Hospitals, Cleveland, OH USA. Electronic address:

Objective: Fibromuscular Dysplasia (FMD) is a rare non-atherosclerotic non-inflammatory vascular disease associated with arterial aneurysms and dissections. The epidemiology of FMD is not well understood. We sought to characterize the epidemiology of FMD utilizing a large aggregated electronic medical record database.

Methods: We used a commercial database (Explorys, IBM Watson), which aggregates data from electronic health records from 26 major integrated healthcare systems in the United States. Fibromuscular dysplasia cases were identified using a unique systemized nomenclature of medical terminology (SNOMED CT) term. We calculated the overall and age-, race-, and sex-based prevalence of FMD, and evaluated sex and race-specific differences in manifestations.

Results: A total of 40,566,670 individuals were active in the database from January 2015 to January 2020. Of these, 4860 had a diagnosis of FMD with an overall prevalence of 12.0 cases per 100,000 individuals. The majority of patients with FMD were female (n=4130, 85.0%), Caucasian (n=3960, 80.5%) and adults aged 18 to 65 years (n=2610, 53.7%). FMD was more common in women (prevalence 18.4 per 100,000) than men (4.0 per 100,000) and among Caucasians (15.8 per 100,000) than African Americans (11.2 per 100,000). Men and African Americans with FMD were more likely to have traditional atherosclerotic risk factors (hypertension, diabetes mellitus type 2, smoking, obesity, hyperlipidemia, chronic kidney disease), and vascular manifestations (stroke, renal infarction, claudication), compared with women and Caucasians. Men with FMD were more likely to have dissection of aorta and renal artery as well as aneurysm of vertebral artery, coronary artery, aorta and iliac artery. African-Americans were more likely to have ruptured aortic aneurysms than Caucasians.

Conclusions: The overall prevalence of FMD in this large aggregated electronic medical record study is estimated at 12.0 per 100,000 persons. FMD is more common in women and Caucasians, with variable characteristics and manifestations.
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http://dx.doi.org/10.1016/j.hrtlng.2020.09.022DOI Listing
April 2021

No-Charge Coronary Artery Calcium Screening for Cardiovascular Risk Assessment.

J Am Coll Cardiol 2020 09;76(10):1259-1262

University Hospitals, Harrington Heart and Vascular Institute, Case Western Reserve University School of Medicine, Cleveland, Ohio. Electronic address:

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http://dx.doi.org/10.1016/j.jacc.2020.06.077DOI Listing
September 2020

Socioeconomic Deprivation and Heart Failure Mortality in the United States.

J Card Fail 2020 12 2;26(12):1106-1107. Epub 2020 Aug 2.

Harrington Heart and Vascular Institute, University Hospitals Cleveland Medical Center and School of Medicine, Case Western Reserve University, Cleveland, OH, USA. Electronic address:

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http://dx.doi.org/10.1016/j.cardfail.2020.07.014DOI Listing
December 2020

Prognostic Value of Left Ventricular Global Longitudinal Strain in COVID-19.

Am J Cardiol 2020 09 3;131:134-136. Epub 2020 Jul 3.

Harrington Heart and Vascular Institute, University Hospital Cleveland Medical Center, Cleveland, Ohio; Department of Medicine, University Hospitals Cleveland Medical Center, Cleveland, Ohio.

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http://dx.doi.org/10.1016/j.amjcard.2020.06.053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332458PMC
September 2020

Dose Titration of Ambulatory Care for Heart Failure: A New Paradigm to Keep Patients Healthy at Home Rather Than Healing in Hospital.

Circ Cardiovasc Qual Outcomes 2019 12 3;12(12):e005952. Epub 2019 Dec 3.

Clinical Transformation Office (G.H.O., P.J.P.), University Hospitals Health System, Cleveland, OH.

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http://dx.doi.org/10.1161/CIRCOUTCOMES.119.005952DOI Listing
December 2019
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