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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 9  |  Issue : 1  |  Page : 19-24

Prevalence and major cardiac causes of cardio-embolic stroke and in-hospital mortality in Eastern Nepal


1 Department of Internal Medicine, Cardiology Unit, Nobel Medical College Teaching Hospital, Biratnagar, Nepal
2 Department of Internal Medicine, Neurology Unit, Nobel Medical College Teaching Hospital, Biratnagar, Nepal

Date of Submission26-Dec-2019
Date of Acceptance31-Jan-2020
Date of Web Publication16-Mar-2020

Correspondence Address:
Dr. Rajesh Nepal
Department of Internal Medicine, Cardiology Unit, Nobel Medical College Teaching Hospital, Biratnagar
Nepal
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/JCPC.JCPC_57_19

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  Abstract 


Background: Cardioembolism accounts for 15%–30% of all ischemic strokes. The study aims to assess conventional and major cardiac causes of cardio-embolic stroke, its prevalence, lesions associated with the side of weakness, and in-hospital mortality. Materials and Methods: Patients with cardio-embolic stroke over 18 months were included in the study. Groups were compared using Chi-square test and Student's t-test. Results: In 384 patients with ischemic stroke, 168 (44%) had a cardio-embolic stroke. Among these 168 cardio-embolic patients, 56% were male and 44% female with a mean age of 69 ± 1 year. Dyslipidemia (72%), hypertension (69%), smoking (34%), and diabetes (33%) were the most prevalent conventional cardiovascular risk factors in these patients. Atrial fibrillation (AF) (71%) was the most common specific cardiac cause for cardio-embolic stroke. Hypertension was present in more than 76%, while dyslipidemia in 66% of patients with AF. Seventeen patients (10%) had in-hospital mortality, while nine (5%) left the hospital against medical advice. The in-hospital mortality rates were not different in AF patients as compared to those with sinus rhythm (59% vs. 41%,P = 0.225). However, patients with left ventricular ejection fraction ≤50% had a higher rate of mortality when compared to patients with normal ejection fraction (P < 0.001). Patients with AF had a higher incidence of left-sided weakness when compared to sinus rhythm (P = 0.049). Conclusion: Hypertension and dyslipidemia were the most prevalent conventional risk factors, while AF was the most common cardiac cause of cardio-embolic stroke. Reduced left ventricular ejection fraction less than 50% was significant predictor of in-hospital mortality in cardio-embolic stroke patients.

Keywords: Atrial fibrillation, cardio-embolic stroke, ischemic stroke, prevalence


How to cite this article:
Nepal R, Choudhary MK, Dhungana S, Katwal S, Khanal SB, Bista M, Monib AK, Kafle DR. Prevalence and major cardiac causes of cardio-embolic stroke and in-hospital mortality in Eastern Nepal. J Clin Prev Cardiol 2020;9:19-24

How to cite this URL:
Nepal R, Choudhary MK, Dhungana S, Katwal S, Khanal SB, Bista M, Monib AK, Kafle DR. Prevalence and major cardiac causes of cardio-embolic stroke and in-hospital mortality in Eastern Nepal. J Clin Prev Cardiol [serial online] 2020 [cited 2020 Apr 7];9:19-24. Available from: http://www.jcpconline.org/text.asp?2020/9/1/19/280821




  Introduction Top


Stroke is the leading cause of disability and the second most common cause of death worldwide.[1] About 15%–30% of all ischemic strokes are cardio-embolic.[1],[2],[3] Atrial fibrillation (AF), ischemic cardiomyopathy, rheumatic mitral valve disease, and left ventricular failure are the most common causes of cardio-embolism. Major sources of embolism have an established causal relationship with stroke, and their identification is usually clinically pertinent.[1],[4] In some reports, about two-third of ischemic strokes were considered as cardio-embolic.[5],[6] AF was the most common source of cardio-embolic stroke,[5],[7] while hypertension was the major associated risk factors.[8] AF-related strokes constitute about 60% of all cardio-embolic strokes.[9] As there are no gold standard diagnostic criteria for cardio-embolic stroke, the presence of a potential major cardiac source of embolism in the absence of significant arterial disease remains the mainstay of clinical diagnosis.

There are no population-based surveys on stroke mortality found in Nepal. According to the WHO estimates, cerebrovascular diseases accounted for 107.5/100,000 deaths (age-standardized death rate) from cerebrovascular diseases in 2002 with a total DALY rate of 543/100,000.[10] A study conducted in Kathmandu reported 88% of ischemic stroke among 281 young patients.[11] Some studies reported that cardio-embolic stroke is less prevalent in South Asia than in Western countries.[12],[13] Nevertheless, some other studies from South Asia reported a high prevalence and incidence of mortality among cardio-embolic stroke patients.[14],[15],[16]

To the best of our knowledge, there is a paucity of data related to the prevalence of cardio-embolic stroke among ischemic stroke patients, cardiac disorder-related cardio-embolic stroke, and hospital mortality in Nepal. Our study aims to assess the prevalence of cardio-embolic stroke among ischemic stroke patients, conventional risk factors, and major cardiac causes for cardio-embolic stroke and outcome in patients admitted in Nobel Medical College.


  Materials and Methods Top


Between January 2017 and June 2018, data of 384 ischemic stroke patients admitted to the Department of Internal Medicine of Nobel Medical College Teaching Hospital were prospectively entered in a stroke registry. Performa was designed to collect patient information, which included demographic variables, cerebrovascular risk factors, and data on clinical and neurological findings, topography, diagnostic studies, and outcome of stroke patients. To be included in the study, patients had to be admitted to the hospital within 48 h of the onset of symptoms. For this study, data from patients with cardio-embolic stroke (n = 168) were included. Patients with hemorrhagic stroke, stoke with major organ failure such as chronic kidney or liver diseases, proven malignancy, recurrent stroke, and age <18 years were excluded from the study.

To diagnose a patient having cardio-embolic stroke requires, the presence of a medium-sized (maximal diameter of the lesion 1.5–3 cm) or large (>3 cm) cerebral infarction, cerebral cortex involvement on the brain computed tomography (CT) and/or magnetic resonance imaging (MRI) scans, sudden (minutes) or acute (hours) onset, stroke onset during ordinary daily activities, peak of deficit at onset, duration of focal neurological deficit >24 h, absence of lacunar clinical syndrome, and identification of a commonly accepted cardiac source of embolus in the absence of confirmatory clinical (ipsilateral carotid bruit) or investigative results (echocardiographic direct imaging plus Doppler ultrasonography, carotid angiography or angio-MRI) of lesions (stenosis ≥50% and/or ulcerated atherosclerotic plaques) in the ipsilateral supra-aortic trunks.

The institutional review committee of Nobel Medical College approved the study protocol. On admission, demographic characteristics, salient features of clinical and neurological examination, results of routine laboratory tests (blood cell count, biochemical profile, serum electrolytes, and urinalysis), chest radiography, and 12-lead electrocardiography were recorded. A brain CT scan was obtained from all patients. In addition to electrocardiography recorded on admission, cardiac investigations included one or various electrocardiographic, Holter monitoring when dysrhythmia was suggested by the patient's medical history, as well as color Doppler echocardiography in all cases.

All cardio-embolic stroke patients were assessed by a cardiologist for the etiological diagnosis of a cardiac source of emboli. The following subgroups were established: atrial arrhythmias (AF and atrial flutter), rheumatic heart disease, prosthetic cardiac valve, nonrheumatic degenerative mitral or aortic valve calcification; ischemic cardiomyopathy (clinical or coronary angiographically proven), dilated cardiomyopathy, cardiac tumors, and endocarditis.

Cardiovascular risk factors were defined as follows

Smoking

It included a history of cigarette smoking (regularly smokes one or more cigarettes per day).

Dyslipidemia

Any of the following values in fasting sample taken within 24 h of the event were as follows: total cholesterol (TC) ≥200 mg/dL, low-density lipoprotein cholesterol (LDL-C) ≥130 mg/dL, triglycerides ≥150 mg/dL, and high-density lipoprotein cholesterol ≤40 mg/dL or patients already on medication for dyslipidemia.

Hypertension

Hypertension included systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg and/or concomitant use of antihypertensive medications.

Diabetes mellitus

It included fasting plasma glucose ≥126 mg/dL or postprandial glucose ≥200 mg/dL or the patients being treated for diabetes.

Alcohol intake

It included weekly consumption of more than 14 units for males and 7 units for female or daily intake of alcohol was taken as significant alcohol consumption.

Statistical analysis

The demographic and laboratory data were analyzed using analysis of variance, and the Bonferroni correction was applied in the post hoc analyses. Categorical variables were reported as a percentage (%) and continuous variables were reported as the mean ± standard error of the mean. Groups were compared using the Chi-square test (cross-tabulation method) for categorical variables and Student's t-test was used for the comparison of continuous variables. P < 0.05 was considered statistically significant with a 95% confidence interval. Data were analyzed using the Statistical Package for the Social Sciences (SPSS) version 17.0 for Windows (SPSS, Inc., Chicago, Illinois, and the USA).


  Results Top


Demographic and study characteristics

Among 384 patients with ischemic stroke, we identified 168 (44%) patients with cardio-embolic stroke [Figure 1]a. The data presented in this study are for 168 patients with cardio-embolic stroke. The mean age of the study population was 69 ± 1 years (32–93 years), while the mean age of males was 67 ± 1 years and female 71 ± 1 years. The mean age of improved patients was 69 ± 1 years, while the mean age of patients with mortality was 67 ± 3 years. Among 168 patients, 95 (56%) were male and 73 (44%) were female. Hypertension was present in 116 (69%). Diabetes was present in 55 (33%). Among 168 cardio-embolic stroke patients, dyslipidemia was reported in 121 (72%) patients. History of alcohol intake was present in 25 (15%), while 57 (34%) were smokers [Table 1]. In the subgroup analysis of patients according to their age, there was no significant difference between patients younger than 65 years or older (data not shown).
Figure 1: Distribution of ischemic stroke (Noncardio-embolic and cardio-embolic origin) (a) and in-hospital outcome in cardio-embolic patients; LAMA, left the hospital against medical advice; n, total number (b)

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Table 1: Baseline characteristics of the 168 patients enrolled (n=168)

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Specific cardiac disorder

Several cardiac conditions have been proposed as potential sources of embolism. Among 168 cardio-embolic strokes, 120 (71%) patients had AF, within which 17 (14%) had lone AF, while 103 (86%) were associated with structural cardiac disease. Sinus rhythm (48, 29%) and left ventricular ejection fraction ≤50% were reported in 66 (40%) patients; among them, dilated cardiomyopathy was found in 45 (27%) patients, ischemic cardiomyopathy in 21 (13%), and rheumatic mitral valve disease in 22 (13%) patients [Table 2].
Table 2: Common cardiac disorders and pathophysiological mechanisms presumptively associated with cardio-embolic stroke

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Among 120 patients with AF, 91 (76%) patients had hypertension and 79 (66%) had dyslipidemia when compared with patients without the above risk factors (P < 0.05). While dyslipidemia was significantly higher among patients diagnosed with ischemic cardiomyopathy, dilated cardiomyopathy and left ventricular ejection fraction ≤50% than patients without the above risk factors. (P < 0.05). Among the potential sources of embolism, sex was not a determinate factor [Table 3].
Table 3: Cardio-embolic sources and risk factors

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Cardiac disorder related to in-hospital mortality and side of weakness

The in-hospital mortality rates were not different in AF patients as compared to those with sinus rhythm (59% vs. 41%, P = 0.225). Patients with dilated cardiomyopathy and left ventricular ejection fraction ≤50% had higher mortality versus patients without the above corresponding diseases (P < 0.001 for all) [Table 4]. Patients with AF had a higher incidence of left-sided weakness when compared to sinus rhythm (P = 0.049). Similarly, patients with ischemic cardiomyopathy had a higher number of left-sided hemiparesis when compared to cardio-embolic stroke patients without ischemic cardiomyopathy [Table 5].
Table 4: Cardiac disorder and its prognosis

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Table 5: Correlation between lesion and side of weakness

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  Discussion Top


There is a paucity of studies on the prevalence of cardio-embolic stroke among ischemic stroke patients, major cardiac causes, and lesion associated with in-hospital mortality of cardio-embolic stroke patients in Nepal. Although some studies had reported the incidence of ischemic stroke and outcome in Nepal,[15],[17],[18],[19] a study reported 36% cardio-embolic stroke prevalence among ischemic stroke based on the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification.[15] The present results showed 44% cardio-embolic stroke prevalence among ischemic stroke based on the TOAST calcification which was higher compared to a study previously done in Nepal, which reported 36% cardio-embolic stroke prevalence among 56 ischemic stroke patients.[15] While there were similar reports from Pakistan (40%),[16] among ischemic stroke patients, all these reports validate that cardiac disorder might be the most common cause of ischemic stroke. The previous study reported a low incidence of cardio-embolic stroke in patients younger than 65 years while the higher rate in older patients.[20] we are trying to state that women are increasingly at risk of stroke, with higher number of (women) suffer from ischemic stroke.[17] In contrast, our result did not found any difference when subgroup analysis was performed according to the age and gender for cardio-embolic stroke, which may be due to a small sample size. Further large studies are required to find an association between age, gender, and cardio-embolic stroke.

Hypertension is a major risk factor for ischemic stroke.[18],[19],[21],[22],[23] Hypertensive patients are at risk for the development of conduction arrhythmia especially. Muscular hypertrophy can interrupt conduction pathways predisposing to AF, which can lead to ischemic stroke.[24] The previous study has reported that hypertension was present in 80% of patients with AF,[25] while hypertension with a risk ratio of 2.8 was a significant independent risk factor for thromboembolic stroke. AF patients with hypertension increases the incidence of stroke by an additional 2–3 times.[26],[27] Our result also correlates with the above finding, as we found that 76% of the patients with AF were hypertensive. The relationship between lipids and stroke is complex. Yaghi and Elkind reported that there is a direct association between cholesterol levels and ischemic stroke and the relationship is most strong for TC and LDL-C.[28] In patients with metabolic syndrome, elevated blood pressure and dyslipidemia were associated with a higher risk of AF in both African-American and native American population.[29] In another study, dyslipidemia was associated with an increased risk of new onset of AF in women but not in men,[30] whereas multiple studies have reported dyslipidemia associated with an increased incidence of heart failure and ischemic cardiomyopathy.[31],[32] In the present study too, hypertension and dyslipidemia were the most common risk factors associated with AF, whereas dyslipidemia associated with dilated cardiomyopathy, Left ventricular ejection fraction ≤50%, and ischemic cardiomyopathy. Thus, optimum control of blood pressure and lipids with drug treatment is also very crucial.

AF is the most important cause of cardio-embolic stroke.[1],[2],[3],[5],[6] AF causes cardio-embolic stroke because it leads to inadequate contraction, and hence, the formation of thrombus within the left atrial appendage. In our current study too, 71% of the patients had an incidence of AF authorizing that AF is the most common cause of cardio-embolic stroke also in Nepal. Arboix et al. too reported a similar finding that patients with cardio-embolic infarction and AF accounted for 76.6% of their total cases.[33] Stroke patients with AF are at high risk of death both at the acute phase of stroke and during the subsequent years after the first acute stroke event. Mortality from cardiac diseases prevailed in the AF group during the acute phase of the stroke.[34] In agreement with the study, even in our study, patients with AF with associated cardiac diseases numerically had a higher rate of in-hospital mortality.

In the present study, among 28 patients treated with clopidogrel, 16 patients were treated in a combination of aspirin for ischemic cardiomyopathy. In the previous study, about 2.5% of patients with acute myocardial infarction experienced a stroke within 2–4 weeks of the infarction.[35] Whereas in the CURE trial, the combination of aspirin and clopidogrel was associated with an RR of 0.89 (P < 0.001); the biggest difference was in the rate of myocardial infarction. This combination therapy has beneficial effects in patients with acute coronary syndromes[36] but carried an increased risk of major bleeding; however, there were no difference in life-threatening or fatal bleeding and no increase in hemorrhagic strokes.[36] The MATCH study reported that patients treated with clopidogrel (75 mg) alone who had an ischemic stroke were at high risk of another event compared to combination therapy with clopidogrel (75 mg) plus aspirin (75 mg).[37] In the present study, patients with cardio-embolic stroke who were not treated with clopidogrel in a combination of warfarin/aspirin had high numerical in-hospital mortality though statically nonsignificant. Further studies are required to clarify the combination therapy effect on cardio-embolic stroke patients.

Salem et al. reported an annual incidence of cardio-embolism of 8% in patients with mitral stenosis and sinus rhythm and 32% in patients with mitral stenosis and AF,[38] while a prospective hospital-based stroke registry with 402 cardio-embolism patients showed an incidence of cardio-embolism of 12.4% in patients with rheumatic mitral valve disease.[39] In the present study, among 168 cardio-embolic stroke patients, 22 (13%) patients source of embolism was rheumatic mitral valve disease; among them, 60% of the patients had AF. Although the overall prevalence of rheumatic heart disease is higher in Nepal, long-term anticoagulation therapy decreases the risk of cardio-embolic stroke, as also seen in the previous studies,[38],[39] which might be the reason for the relatively small number of patients with rheumatic mitral valve disease in our study.

Among patients with dilated cardiomyopathy, stroke is a common sequel, whereas left ventricular dysfunction and older age are both independent predictors of an increased risk of stroke.[40] De Jong et al. reported that patients with cardio-embolic stroke had the highest mortality, among which recurrent stroke and heart failure were an important cause of death.[41],[42] In agreement with the above report, in our current study, patients with dilated cardiomyopathy and left ventricular ejection fraction ≤50% had the highest rate of-hospital mortality.

Approximately 80% of emboli primarily lodge into the anterior circulation of the brain (middle cerebral artery) and 20% into the posterior circulation.[43] In the present study for the first time, we have reported that patients with AF have more incidences of left-sided hemiparesis compared to sinus rhythm, whereas patients with AF associated with ischemic cardiomyopathy too have a higher rate of left-sided weakness compared to the patient not suffering from ischemic cardiomyopathy. This may be due to easy access for thrombus to travel straighter path in the right carotid artery than the long and double bent path of the left carotid artery.

In the previous study, a higher incidence of mortality was reported from Nepal, and among 20 cardio-embolic patients, 3-month mortality was recorded in 12 (60%) patients.[15] While in our current study, in-hospital mortality was 10%, and leave against medical advice (LAMA) were nine (5%) patients [Figure 1]b. Among nine LAMA patients, eight were above 65-year-old, with very poor prognosis, in which case death can be assumed at home. Thus, even in our study, high in-hospital mortality was recorded among cardio-embolic patients.

There are a few limitations to the present study. First, the study was performed at the tertiary care center in Eastern Nepal, and the results cannot be generalized to the public and could just represent the patients with the referral bias. Second, the study shows the presence of admission bias, as only sick patients requiring urgent admission and medical attention were admitted. Third, the actual outcome of LAMA patients could not be ascertained.


  Conclusion Top


Hypertension and dyslipidemia were the most prevalent conventional cardiovascular risk factors, while AF was the most common cardiac cause of cardio-embolic stroke. Patients associated with cardiac diseases such as dilated cardiomyopathy and ejection fraction ≤ 50% were significant predictors of in-hospital mortality in cardio-embolic stroke patients. These data may help the clinician to establish an early prognosis of this stroke subtype more accurately.

Acknowledgments

The authors express gratitude to the staff of the Coronary Care Unit, Nobel Medical College, for their valuable cooperation in the preparation of this manuscript.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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