J Cardiovasc Dis Med 2019 Inno Journal of Volume 2.1 and Medicine

Non- Scarring: Could it Serve as a Possible Biomarker for Atrial ?

Gadhia R1* 1Houston Methodist Neurological Institute, USA 2Texas A M University, USA Volpi J1 2 3University of Virginia School of Medicine, USA HooksNorkiewicz R3 Z

Abstract Article Information In a series of patients with cerebrovascular disease, Background: Article Type: Research delayed enhancement cardiac magnetic resonance (DE-CMR) detected Article Number: JCDM116 non-coronary artery disease (non-CAD) scarring in 15.3% of stroke Received Date: 03 April, 2019 patients and 4.8% in TIA patients [1]. One hypothesis for this trend Accepted Date: 12 April, 2019 was that high incidence of non-CAD scarring may be a result of small Published Date: 19 April, 2019 biomarker for non- CAD scarring, earlier diagnosis and treatment could *Corresponding Author: Dr. Rajan R Gadhia, Houston potentiallymicroemboli decrease and a biomarker the number for of atrial cryptogenic fibrillation embolic [2]. Ifstrokes validated through as a Methodist Neurological Institute, USA. Tel: 2815075166; earlier anticoagulation therapy and decrease the economic burden of Fax: 7137937019; Email: rrgadhia(at)houstonmethodist.org stroke-related treatment and healthcare costs [3,4]. Citation: Gadhia R, Norkiewicz Z, Volpi J, Hooks R (2019) Methods: EPIC Slicer dicer was utilized to search for “stroke” and Non-Coronary Artery Disease Scarring: Could it Serve as a cardiac MRI”. 87 patients’ medical records were accessed in order to Possible Biomarker for ? J Cardiovasc Dis obtain information regarding the factors stated previously, the presence Med. Vol: 2, Issu: 1 (04-07). were evaluated to see if there was an association between non-CAD Copyright: © 2019 Gadhia R. This is an open-access of atrial fibrillation, and cMRI results. Patients’ medical histories article distributed under the terms of the Creative Commons consumption, diabetes, hypertension, hyperlipidemia, renal disease, Attribution License, which permits unrestricted use, historyscarring ofand myocardial atrial fibrillation. infarction Factors (MI), such seizures, as gender, and smoking, race was alcohol also distribution, and reproduction in any medium, provided the original author and source are credited. analyzed to see if these factors had any effect on the prevalence of non-

CADResults: scarring Large and differences atrial fibrillation. in the occurrences of non-CAD and CAD scarring were seen with gender, smoking, diabetes, hypertension, hyperlipidemia, renal disease, history of MI, and seizures in patients morewith no non-CAD documented and CAD atrial scarring fibrillation. occurrences There werewhen more smoking, non-CAD diabetes, and CAD scarring males with no atrial fibrillation compared to females and inor the hypertension absence of wasrenal present disease, with history no of atrial MI, and fibrillation. seizures; Non-CAD these trends and withCAD scarringrenal disease occurrences and seizures with no were atrial unexpected. fibrillation were more prevalent Conclusion: Even though trends were observed with the various factors, scarring, and the presence or absence of atrial fibrillation, our study thisfound patient no statistically sample, we significant saw no association evidence that between suggests non-CAD certain scarring factors impact non-CAD or CAD scarring with and without atrial fibrillation. In the unexpected scarring trend seen with no renal disease or seizures present.and atrial fibrillation. Future studies could be conducted to explore Keywords:

Non-Coronary Artery Disease, EPIC Slicer dicer, Atrial Fibrillation, cMRI. www.innovationinfo.org

Introduction males and females, occurrences of CAD scarring with and of non-CAD scarring with and without atrial fibrillation in occurrences of non-CAD scarring with and without atrial of deathIn 2013, [3]. approximately Several risk 6.5factors million for people stroke worldwide include Atrial died without atrial fibrillation in current and former smokers, due to stroke, making stroke the fifth ranked global cause and diabetes [5]. In addition to stroke, 17.3 million people drinkersfibrillation and in currentnon-drinkers, and former occurrences smokers, of occurrences non-CAD worldwideFibrillation died (AF), due hypertension, to cardiovascular hyperlipidemia, disease (CVD) smoking, [3]. of CAD scarring with and without atrial fibrillation in and non-drinkers, occurrences of CAD scarring with and failure, chronic kidney disease, and coronary artery disease scarring with and without atrial fibrillation in drinkers Common outcomes of CVD include atrial fibrillation, heart (CAD), which can develop due to factors such as hypertension, occurrences of non-CAD scarring with and without atrial without atrial fibrillation in diabetics and non-diabetics, stroke and CVD deaths per year continue to remain high as dyslipidemia, smoking, or diabetes [6,7]. The number of the prevalence of stroke risk factors and CVD related health withfibrillation and without in diabetics hypertension, and non-diabetics, occurrences occurrences of non-CAD of CAD scarring with and without atrial fibrillation in patients and without hypertension, occurrences of CAD scarring issues continue to increase, especially atrial fibrillation scarring with and without atrial fibrillation in patients with [3,6]. Atrial fibrillation is the most common and without hyperlipidemia, occurrences of non-CAD scarring byincreases techniques the risk such of stroke as in-hospital by five [8]. monitoring, Detection rate Insertable of atrial with and without atrial fibrillation in patients with and fibrillation remains low with 0-25% of incidences detected Cardiac Monitors (ICMs), Serial Electrocardiography (ECG), without hyperlipidemia, occurrences of CAD scarring with with and without atrial fibrillation in patients with and effective biomarker is needed to increase the detection rate renal disease, occurrences of non-CAD scarring with and and cardiac magnetic resonance imaging (cMRI) [2,4]. An and without atrial fibrillation in patients with and without or recurrent stroke prevention. Unfortunately, nearly a third disease, occurrences of CAD scarring with and without of atrialpatients fibrillation who present and lead with to earlierembolic treatment strokes andof unknown primary without atrial fibrillation in patients with and without renal source are discharged on antiplatelet therapy, which is an MI, occurrences of non-CAD scarring with and without atrial fibrillation in patients with and without history of occurrences of CAD scarring in patients with and without ineffectiveA possible regimen biomarker for paroxysmal could be AF.discovered using cMRI, an imaging technique that can detect cardiac pathologies seizures,atrial fibrillation occurrences in patients of non-CAD with and scarring without in historypatients of with MI, such as heart arrhythmia and myocardial scarring - scar and without seizures, occurrences of CAD scarring with tissue that forms when muscular tissue of the heart dies American, and Asian race, and occurrences of non-CAD and without atrial fibrillation in patients of white, African due to [2,9]. cMRI could be used to of white, African American, and Asian race. All data was Transientdiscover a Ischemic possible Attackbiomarker (TIA) of patients AF due into thisfindings study, from non- a thenscarring sent withfor statistical and without analysis atrial to determine fibrillation if inany patients trends CADrecently scarring published was detected 2014 study. in 15.3% Of 85 andischemic 4.8% strokein stroke and and 21 approximately 3 times more prevalent in stroke patients Resultsbetween the various bar graphs were statistically significant. thanTIA patients, TIA patients, respectively non-CAD [2]. scarring Since could non-CAD possibly scarring be linked was was approximately double the percentage of CAD scarring From all 87 patients and 43 scarring occurrences, there CVD.to ischemic If non-CAD stroke scarring [2]. Thus, is found non-CAD to be a scarringstrong predictor could be for a biomarker for atrial fibrillation, a risk factor for stroke and inoccurrences scarring occurrences with atrial and fibrillation similar thanpatterned non-CAD graphs scarring were stroke, the number of global stroke deaths per year, and the occurrences with atrial fibrillation. The largest differences underlying atrial fibrillation, this would decrease the risk of noted a few trends with gender, race, diet, renal dysfunction, seizuresseen in factors and smoking with no whenatrial comparedfibrillation. with In our scarring cohort, and we Methodsamount of money spent on stroke related healthcare [3,10]. CVD. In looking through the literature, there are a number EPIC Slicer dicer was utilized to search for “stroke” and of studies that have sought to try to explain the generally “cardiac MRI” which gave yield to 87 patients. Each patient’s observed trends. The non-CAD and CAD scarring graphs for medical records were accessed in order to examine the studied factors (gender, smoking, alcohol consumption, more males with scarring than females. The scarring trend diabetes, hypertension, hyperlipidemia, renal disease, observedgender with in nomales atrial is fibrillationlikely from revealed differences that in there baseline were history of Myocardial Infarction (MI), seizures, and race), results were analyzed to determine if the patient had CAD menrisks. had A 10-year myocardial study scarring conducted whereas in the the US prevalence consisting of scarring,the presence non-CAD of atrial scarring, fibrillation, or no scarring and cMRI at results.all. Once CMRI data 1840 participants with no CVD discovered that 12.9% of was gathered from all 87 patients, the following bar graphs were developed: occurrences of CAD scarring with and hypertension,scarring in women more womenwas 2.5% had [11]. low triglyceridesIn yet another and study higher of 1527 patients aged 20 years or older, fewer women had without atrial fibrillation in males and females, occurrencesJ Cardiovasc DisHDL, Med and2019 women were less likely to smoke [12]. These05 www.innovationinfo.org disproportionate baseline factors could explain the trend Both the non-CAD and CAD scarring graphs for smoking, observed in males that place them at a higher risk for CVD along with increasing their risk for developing CAD, which larger scarring occurrences when the factor was present. The could potentially explain the higher CAD scarring in men. diabetes, and hypertension with no atrial fibrillation had It is important to note, however, that this study also makes partially exhibited the same trend as the smoking, diabetes, note that of all women, mostly non-Latino black women had andscarring hypertension graphs for hyperlipidemiagraphs. The CAD with noscarring atrial fibrillationgraph of a higher risk of hypertension and diabetes when compared with non-Latino white women, non-Latino white men, and was more CAD scarring occurrences with the factor present. However,hyperlipidemia the non-CAD with no atrialscarring fibrillation graph ofshowed hyperlipidemia that there non-Latino black men [12]. Considering that approximately number of occurrences when the factor was present and have8 of the shown 36 females a higher in our scarring cohort are occurrence non-Latino with black no women atrial absent.with no atrial fibrillation showed that there was an equal and 25% of these women have CAD scarring, the trend might proportion of non-Latino white women and non-Latino blackfibrillation women. for Ifmen the thanproportion women of due non-Latino to the rather white unequal women non-CADFor the and patients CAD scarring with renal were disease,higher when history the offactor MI, was and and non-Latino black women were approximately equal, notseizures present; without this is atrial the opposite fibrillation, trend the seen occurrences with those patient’s of both the difference between scarring occurrences with no atrial hat have history of smoking, diabetes, and hypertension. Several past studies do not appear to support the trend The trend observed for gender in this study could have observed with both the non-CAD and CAD scarring graphs alsofibrillation been affected for men by and depression. women might One study have that been analyzed smaller. the effect of depression on CVD risk factors discovered that women who were depressed had higher incidences of insulin (UAE)with no discovered atrial fibrillation that menfor renal and disease.women A withretrospective chronic resistance, low high-density lipoprotein (HDL), and high kidneystudy involving disease stages491 adults 3-5 also from had the diabetes, United Arab hypertension, Emirates low-density lipoprotein (LDL) compared to women who dyslipidemia, as well as another CVD risk factors [1]. Since were not depressed. This trend held true for men who were this study indicated that there may be an association with depressed who also had an increased likelihood of having chronic kidney disease stages 3-5 and several CVD risk hypertension and smoking compared to men who were not factors, one would predict that there were would be more depressed [13]. Thus, if there were more depressed men instances of CAD and CAD scarring for people with chronic than depressed women in our study, there is a possibility kidney disease stages 3-5 compared to those with no kidney that the chances of developing CAD could have been higher. disease. Interestingly, within our study population, we found a higher incidence of CAD scarring in people with no trend. This in turn could have had an influence on the scarring renal disease. Moreover, another study investigating CAD in renal transplant recipients discovered that CAD was indicated that vegetable variety could affect CAD [14]. This most severe in people on chronic dialysis, followed by renal Furthermore, a recent study looking at diet trends transplant patients, and lastly people without existing renal an inverse relationship between vegetable variety and the study that included 38,981 adults showed that there was that there would be less CAD scarring instances with those whoimpairment have no [16]. chronic One kidney could, disease.based on Again, prior surprisingly,studies, theorize this theprevalence high scarring of CAD trend [2]. The seen study with also smokers revealed could that potentially smokers was not observed with the renal disease CAD scarring graph havedid not been tend affected to eat by vegetables vegetable of variety. a wide Yet variety another [2]. study Thus, looking at diet trends conducted in Western India found a has limitations, and sampling bias could have also impacted higher prevalence of CVD risk factors when they skipped thein patients scarring withouttrend. Patients atrial fibrillation. with renal Ourdisease study of a certainly certain breakfast [15]. Those that skipped breakfast had the highest severity are not able to have cMRI’s performed, thus, this odds of developing diabetes, followed by hypertension and study likely could have excluded a large amount of people smoking as a habit [15]. Although certainly a stretch, it is who could have had CAD or non-CAD scarring. possible that if the people in our study skipped breakfast on a regular basis, then they could have had a higher chance Similarly, to what we found in patients with renal disease, of developing CVD, then CAD, and possibly CAD scarring; patients with history of seizure with non-CAD and CAD this would have impacted the high scarring trend seen with smokers compared to former smokers, diabetics compared of what is reported in recent studies. One study, consisting of to non-diabetics, and people with hypertension compared to scarring, but without atrial fibrillation had the opposite trend people without hypertension. The trend in the CAD scarring had diffusion hyperintense lesions (DHLs) in the perforating arteries677 patients [17]. with These seizures, patients found also that had 3.4% a higher of these likelihood patients have been affected by the depression study that could have impactedwith no atrial the fibrillationgender-scarring graph trend.for hyperlipidemia Since high cholesterol could also is a CVD risk factor, if there was a large number of depressed thisof developing study indicates possible that outcomes there mightof CVD, be specifically an association atrial women in the current study, they could have had low HDL fibrillation and CAD, than patients without DHLs [17]. Since and high LDL, which might have increased their chance of patients in our study who had seizures may not have had developing CAD, as well as CAD scarring [3,13]. DHLsbetween and DHLs CAD. and This two in turnspecific could possible have impactedoutcomes theof CVD, low

J Cardiovasc Dis Med 2019 06 www.innovationinfo.org occurrences of CAD scarring in patients without atrial 5. Benjamin EJ, Virani SS, Callaway CW, Chamberlain AM, Chang AR, et al.

. the expected low number of scarring occurrences in those (2018) Heart disease and stroke statistics-2018 update: a report from fibrillation in those with a history of seizures. Finally, as for the American HeartCardiovascular Association. risk Circulation factors and 137: disease e67-e492 in women. Med . was observed in our cohort. We were not surprised given 6. Gill SK (2015) thatwithout myocardial history of scarring MI and atrialgenerally fibrillation, forms awhen similar cardiac trend 7. Clin North Am 99: 535-552 Prevalence and muscle cells die in the setting of as seen with clustering of cardiovascular disease risk factors among Tibetan adults in Xu S, Jiayong Z, Li B, Zhu H, Chang H, et al. (2015) .

8. China: a population-based study. PLoS One Stroke10: e0129966 prevention in atrial Discussion . myocardial infarction [12]. Li YG, Lee SR, Choi EK, Lip GY (2008) Although our results suggest that the presence of certain fibrillation: focus on Asian patients. Korean Circ J 48: 665-684Physiological . factors could be related to CAD or non-CAD scarring and not 9. Richardson WJ, Clarke SA, Quinn TA, Holmes JW (2015) implications of myocardial scar structure. Compr Physiol 5: 1877-1909Atrial

10. Santos JV, Pereira J, Pinto R, Castro PM, Azevedo E, et al.. (2017) having atrial fibrillation, we found no statistical significance fibrillation as an ischemic stroke clinical and economic burden modifier: between atrial fibrillation in direct relationship with CAD 11. a 15-year nationwide study. Value Health 20: 1083-1091 scarring. Additionally, our cohort failed to find a link between Prevalence of and factors associated with myocardial scar in a U.S. Turkbey EB, Nacif MS, Guo M, McClelland. RL, Teixeira PBRP, et al. (2015) non-CAD scarring and atrial fibrillation. The need for a Gender morebiomarker focused, for atrial randomized fibrillation controlled has a significant studies potentialare needed for Cohort. JAMA 314: 1945-1954 tobenefit better in primarytest for theseand secondary possible strokebiomarkers. prevention. Additionally, Larger, 12. Kanchi R, Perlman SE, Chernov C, Wu W, Tabaei BP, et al. (2018) subgroups such as ours with renal dysfunction, seizure, or and race disparities in cardiovascular disease .risk factors among New York City adults: New York City Health and Nutrition Examination 13. Survey 2013-2014. J Urban Health 95: 801-812 with scarring, warrant further review. Symptoms of depression in young adulthood is associated with specific demographic factors which had a trend to correlation unfavorableKlakk H, Kristensen clinical and PL, behavioral Andersen cardiovascular LB, Froberg K,disease Moller risk NC, factors. et al. References (2018) . 1. Chronic kidney disease 14. Greater vegetable variety and amount Prev Med Rep 22: 209-215 in patients at high risk of cardiovascular disease in the United Arab Al-Shamsi S, Regmi D, Govender RD (2018) . Conrad Z, Raatz S, Jahns L (2018) . are associated with lower prevalence of coronary heart disease: National Emirates: a population-based study. PLoS one. 13: e0199920 Cardiac 15. Health and Nutrition Examination Survey, 1999-2014.Skipping Nutr J 17: breakfast 67 . 2. CerebrovascularBaher A, Mowla A, Kodali S, Polsani VR,. Nabi F, et al. (2014) Sharma K, Shah K, Brahmbhatt P, Kandre Y (2018) MRI improves identification of etiology of acute ischemic stroke. and the risk of coronary artery disease.Gout andQJM the111: risk 715-719 of incident atrial 3. Diseases 37: 277-284 Heart . 16. Singh JA,. Cleveland JD (2018) Benjamin EJ, Blaha MJ, Chiuve SE, Cushman M, Das SR, et al. (2017) fibrillation in older adults: a study of US Medicare data. RMD Open 4: 4. Sannadisease T, and Diener stroke HC, statistics- Passman 2017 RS, update. Di Lazzaro Circulation V, Bernstein 135: e146-e603 RA, et al. 17. e000712 Small hyperintensities in the area of the perforating arteries in patients . Izutsu N, Fujimoto Y, Yamada N, Kajikawa. R, Yoshimura K, et al. (2018) (2014) Cryptogenic stroke and underlying atrial fibrillation. The New England Journal of Medicine 370: 2478-2486 with seizure. Eur Neurol 79: 221-227

Citation: Gadhia R, Norkiewicz Z, Volpi J, Hooks R (2019) Non-Coronary Artery Disease Scarring: Could it Serve as a Possible Biomarker for Atrial Fibrillation? J Cardiovasc Dis Med. Vol: 2, Issu: 1 (04-07).

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