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      Outcomes after transcatheter aortic valve replacement in cancer survivors with prior chest radiation therapy: a systematic review and meta-analysis

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          Abstract

          Background

          Cancer survivors with prior chest radiation therapy (C-XRT) frequently present with aortic stenosis (AS) as the first manifestation of radiation-induced heart disease. They are considered high-risk for surgical valve replacement. Transcatheter aortic valve replacement (TAVR) is as an attractive option for this patient population but the outcomes are not well established in major clinical trials. The authors performed a systemic review and meta-analysis of clinical studies for the outcomes after TAVR in cancer survivors with prior C-XRT.

          Methods

          Online databases were searched from inception to April 2020 for studies evaluating the outcomes of TAVR in patients with and without C-XRT. We analyzed the pooled estimates (with their 95% confidence intervals) of the odds ratio (OR) for the all-cause mortality at 30-day and 1-year follow-ups, 4-point safety outcomes (stroke, major bleed, access-related vascular complications and need for a pacemaker), a 2-point efficacy outcome (mean aortic valve gradient and left ventricular ejection fraction) and worsening of congestive heart failure (CHF). Four studies were included following 2054 patients with and without prior C-XRT exposure (164 patients and 1890 patients respectively).

          Results

          The C-XRT group had similar 30-day mortality compared to the control group (OR 1.29, 95% CI 0.64 to 2.58, p = 0.48). The 1-year mortality was higher in the C-XRT group (OR 1.97, CI 1.15 to 3.39, p = 0.01). Apart from higher congestive heart failure (CHF) exacerbation in the C-XRT group (OR 2.03, CI 1.36 to 3.04, p = 0.0006), TAVR resulted in similar safety and efficacy outcomes in both groups.

          Conclusion

          TAVR in the C-XRT group has similar 30-day mortality, safety, and efficacy outcomes compared to the control group; however, they have higher 1-year mortality and CHF exacerbation. Including an oncologist to the cardiology team who considers cancer stage in the decision-making process and applying additional preoperative scores such as frailty indices may refine the risk assessment for these patients. The quality of analyzed data is modest, warranting randomized trials to assess the true benefits of TAVR in these patients.

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          Most cited references33

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          Updated standardized endpoint definitions for transcatheter aortic valve implantation: the Valve Academic Research Consortium-2 consensus document.

          The aim of the current Valve Academic Research Consortium (VARC)-2 initiative was to revisit the selection and definitions of transcatheter aortic valve implantation (TAVI) clinical endpoints to make them more suitable to the present and future needs of clinical trials. In addition, this document is intended to expand the understanding of patient risk stratification and case selection. A recent study confirmed that VARC definitions have already been incorporated into clinical and research practice and represent a new standard for consistency in reporting clinical outcomes of patients with symptomatic severe aortic stenosis (AS) undergoing TAVI. However, as the clinical experience with this technology has matured and expanded, certain definitions have become unsuitable or ambiguous. Two in-person meetings (held in September 2011 in Washington, DC, USA, and in February 2012 in Rotterdam, the Netherlands) involving VARC study group members, independent experts (including surgeons, interventional and non-interventional cardiologists, imaging specialists, neurologists, geriatric specialists, and clinical trialists), the US Food and Drug Administration (FDA), and industry representatives, provided much of the substantive discussion from which this VARC-2 consensus manuscript was derived. This document provides an overview of risk assessment and patient stratification that need to be considered for accurate patient inclusion in studies. Working groups were assigned to define the following clinical endpoints: mortality, stroke, myocardial infarction, bleeding complications, acute kidney injury, vascular complications, conduction disturbances and arrhythmias, and a miscellaneous category including relevant complications not previously categorized. Furthermore, comprehensive echocardiography recommendations are provided for the evaluation of prosthetic valve (dys)function. Definitions for the quality of life assessments are also reported. These endpoints formed the basis for several recommended composite endpoints. This VARC-2 document has provided further standardization of endpoint definitions for studies evaluating the use of TAVI, which will lead to improved comparability and interpretability of the study results, supplying an increasingly growing body of evidence with respect to TAVI and/or surgical aortic valve replacement. This initiative and document can furthermore be used as a model during current endeavors of applying definitions to other transcatheter valve therapies (for example, mitral valve repair). Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
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            Valvular dysfunction and carotid, subclavian, and coronary artery disease in survivors of hodgkin lymphoma treated with radiation therapy.

            The majority of patients with Hodgkin lymphoma are young and highly curable. This necessitates concern for prevention, diagnosis, and optimal management of potential treatment-related complications. To identify and quantify the incidence of and factors contributing to long-term cardiac and vascular complications after radiation therapy for Hodgkin lymphoma. Retrospective study comparing patients treated from 1962 to 1998 at a university-based referral center with a matched general population. Four hundred fifteen consecutive patients who fulfilled the inclusion criteria of a minimum 2-year follow-up (median, 11.2 years) and whose radiation fields included the heart or carotid or subclavian arteries. Multivariable analyses of potential risk factors and observed-to-expected ratios for cardiac valve surgery, coronary artery bypass graft surgery, percutaneous coronary intervention, or both based on Surveillance, Epidemiology, and End Results (SEER) and National Hospital Discharge Survey (NHDS) data. Forty-two patients (10.4%) developed coronary artery disease at a median of 9 years after treatment, 30 patients (7.4%) developed carotid and/or subclavian artery disease at a median of 17 years after treatment, and 25 patients (6.2%) developed clinically significant valvular dysfunction at a median of 22 years. The most common valve lesion was aortic stenosis, which occurred in 14 valves. The observed-to-expected ratio for valve surgery was 8.42 (95% confidence interval [CI], 3.20-13.65) and the observed-to-expected ratio for coronary artery bypass graft surgery or percutaneous coronary intervention was 1.63 (95% CI, 0.98-2.28). At least 1 cardiac risk factor was present in all patients who developed coronary artery disease. The only treatment-related factor associated with the development of coronary artery disease was utilization of a radiation technique that resulted in a higher total dose to a portion of the heart (relative risk, 7.8; 95% CI, 1.1-53.2; P =.04). No specific treatment-related factor was associated with carotid or subclavian artery disease or valvular dysfunction. Freedom from any cardiovascular morbidity was 88% at 15 years and 84% at 20 years. Among patients treated with radiation therapy for Hodgkin lymphoma, there are statistically higher than expected rates of valve surgery and coronary revascularization procedures over the next 10 to 20 years. Coronary vascular disease is associated with higher radiation doses and traditional coronary heart disease risk factors. Noncoronary vascular disease and clinically important valvular dysfunction are less well understood complications at 15 to 20 years after radiation, requiring surveillance and further study.
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              Radiation-Induced Heart Disease: Pathologic Abnormalities and Putative Mechanisms

              Breast cancer is a common diagnosis in women. Breast radiation has become critical in managing patients who receive breast conserving surgery, or have certain high-risk features after mastectomy. Most patients have an excellent prognosis, therefore understanding the late effects of radiation to the chest is important. Radiation-induced heart disease (RIHD) comprises a spectrum of cardiac pathology including myocardial fibrosis and cardiomyopathy, coronary artery disease, valvular disease, pericardial disease, and arrhythmias. Tissue fibrosis is a common mediator in RIHD. Multiple pathways converge with both acute and chronic cellular, molecular, and genetic changes to result in fibrosis. In this article, we review the pathophysiology of cardiac disease related to radiation therapy to the chest. Our understanding of these mechanisms has improved substantially, but much work remains to further refine radiation delivery techniques and develop therapeutics to battle late effects of radiation.
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                Author and article information

                Contributors
                sharmau@buffalo.edu
                Journal
                Cardiooncology
                Cardiooncology
                Cardio-oncology
                BioMed Central (London )
                2057-3804
                14 July 2020
                14 July 2020
                2020
                : 6
                : 8
                Affiliations
                [1 ]GRID grid.273335.3, ISNI 0000 0004 1936 9887, Department of Medicine, Division Cardiology, , Jacob’s School of Medicine and Biomedical Sciences, ; 875 Ellicott Street, Suite 7030, Buffalo, New York, 14203 USA
                [2 ]GRID grid.417118.a, ISNI 0000 0004 0435 1924, Department of Internal Medicine, , William Beaumont Hospital, ; Royal Oak, MI USA
                Author information
                http://orcid.org/0000-0003-0476-2523
                Article
                62
                10.1186/s40959-020-00062-y
                7359474
                32685198
                ad366a8c-dd57-4a11-8063-3703f17b06d7
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 9 May 2020
                : 2 July 2020
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100000050, National Heart, Lung, and Blood Institute;
                Award ID: K08HL131987
                Award Recipient :
                Categories
                Research
                Custom metadata
                © The Author(s) 2020

                radiation,cancer survivior,tavr,meta-analysis
                radiation, cancer survivior, tavr, meta-analysis

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