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July2014 Vol.51 Issue:      3 (Supp.) Table of Contents
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Impact of Heart Failure on Ischemic Stroke Severity and Short Term Prognosis: An Egyptian Study

Taha K. Aloush, Lobna M. El-Nabil, Mahmoud Haroon,

Nahed Salah, Maha A. Nada, Hosam Azmy

Department of Neurology, Ain Shams University; Egypt


ABSTRACT

Background: Heart failure with impaired systolic function is thought to be associated with severer stroke presentation and increased incidence of long-term mortality and morbidity after ischemic stroke. Objective: To assess the impact of heart failure on ischemic stroke severity and short-term prognosis and to explore if this group has specific features on imaging studies of the intra- or extra-cranial vessels. Methods: The study included two hundreds patients diagnosed with acute ischemic stroke within 3days in Stroke unit, Ain Shams University specialized hospital. They underwent clinical, laboratory investigations and radiological examination including echocardiography, magnetic resonance image (MRI) of the brain and magnetic resonance arteriography (MRA). They were reassessed after one month using National Institute of Health Stroke Scale (NIHSS). Results: Heart failure (HF) patients were 11% of the whole sample. They tended to have partial anterior circulation infarcts (62.5%), 87.5% had Leukoaraiosis which is higher than that for the whole group. HF patients tended to have significant intracranial vessel stenosis (87.5% of patients compared to 79.1% for the whole sample), they also tended to score higher on the NIHSS compared to  the whole group at admission and at follow up).Conclusion: Heart failure tends to have a negative impact on the severity and prognosis of ischemic stroke patients. [Egypt J Neurol Psychiat Neurosurg.  2014; 51(3): 295-301]

Key Words: ischemic stroke, heart failure, NIHSS, MRA

Correspondence to Lobna Mohammad Elnabil, Department of Neurology, Ain Shams University, Cairo, Egypt. Tel.: +201001120127    Email: lobna_alnabil@yahoo.com.





INTRODUCTION

 

Different cardiac diseases have their own impact on severity, subtyping and prognosis of stroke.1Heart failure is a complex syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the heart to function as a pump to support a physiological circulation. The incidence of heart failure increases with advancing age.2 Coronary artery disease is the commonest cause of heart failure in western countries (accounting for 40% of cases), whereas in other areas, hypertensive and valvular heart disease has greater contribution. Heart failure with impaired systolic function was documented to be associated with severer stroke and increased incidence of long-term mortality and morbidity after ischemic stroke.3

Aim of work: To assess the impact of heart failure on ischemic stroke severity and short-term prognosis and to explore if this group has specific features on imaging studies of the intra- or extra-cranial vessels.

 

PATIENTS AND METHODS

 

This study is a prospective hospital based study. Two hundreds acute ischemic stroke patients were recruited from the stroke unit at Ain Shams University Specialized Hospital, Cairo, Egypt. Diagnosis was based on clinical history, examination and confirmed by magnetic resonance image (MRI). Inclusion criteria was; acute ischemic stroke patients within 3 days from the onset, patients diagnosed clinically to have ischemic stroke defined as “rapidly developing clinical symptoms and/or signs of focal, and at times global, disturbances of cerebral function, lasting more than 24 hours or leading to death with no apparent cause other than that of vascular origin4”, and CT or gradient echo MRI does not show areas of hemorrhage. Exclusion criteria were; intracerebral hemorrhage, venous thrombosis, and structural lesions, such as ruptured arteriovenous malformations.

Each patient was submitted to full history taking; either from the patient or the family, including past medical history. Complete neurological examination was done, together with scoring using the National Institute of Health Stroke Scale (NIHSS) score on admission to the emergency department and before discharge. The type of ischemic stroke was determined using the Modified Oxfordshire classification into total anterior, partial anterior, lacunar and posterior circulation stroke.5Patients were followed up by NIHSS after 1 month.

All patients were subjected to (a) CT brain in emergency room, (b)  Carotid duplex for the extracranial vessels,   significant carotid stenosis was defined as narrowing of the lumen of ≥ 70%1, (c)Electrocardiography (ECG),(d) Transthoracic echocardiography, where heart failure was diagnosed if ejection fraction (EF) was ≤40%3, and (e) Brain MRI;stroke protocol in Ain Shams University Specialized Hospital, was done within first 3 days of admission, using a 1.5 tesla head coil (General Electric machine “Sigma Prospeed LX”), including T1, T2, T2-star, FLAIR, diffusion and magnetic resonance angiography (MRA) images. Stenosis (segmental flow gap or luminal stenosis >50%) or occlusion (nonvisualized vessel segment with absent distal flow) were assessed in proximal middle cerebral arteries, proximal anterior cerebral arteries, intracranial internal carotid artery, proximal posterior cerebral arteries, vertebral arteries, and the basilar artery. Stenosis was quantified using the measurement tools of the native MRI viewer according to standard method  (WASID method), by comparing the diameter of the stenosed area and the diameter (D) of the proximal vessel just proximal to the stenosed vessel and applying the equation {Percent stenosis= [1-(Dstenosis/Dnormal)] × 100%} where percentage ≥ 25% were taken as positive value.6 Arterial lesions corresponding to the location/territory of the recent infarct on diffusion-weighted imaging were considered symptomatic.

 

Statistical Analysis

The data were coded, entered and processed on computer using SPSS (version 15). The level P < 0.05 was considered the cut-off value for significance. Chi-Square test (χ2) was used to test the association variables for categorical data. Fisher exact test was performed in table containing value less than 5. Student's t-test was used to assess the statistical significance of the difference between two population means in a study involving independent samples. The Wilcoxon signed-rank test to assess the statistical significance of the difference between two populations in a study involving matched or paired samples.

 

RESULTS

 

This study included 200 patients, with an age range between 23-90 years with a mean and a standard deviation of 61.87±12.65. They were 118(59%) males and 82(41%) were females. Patients showed a median NIHSS score of 8 with IQR of 5-14 at admission (200 patients) and 4 with IQR of 2-8 at 1 month follow-up (174 patients who are still alive).  At 1-month follow-up, 26 patients (13%) were dead.

Out of 200 patients, only 148 patients had an MRI brain according to Ain Shams University stroke protocol. Of those, 51patients (34.5%) had lacunar infarction, 65 patients (43%) had partial anterior circulation infarction, 25 patients (16.9%) had posterior circulation infarction and 7 patients (4.7%) had total anterior circulation infarction. The detailed descriptive data of the all patients are summarized in Tables (1) and (2).

Sixteen out of the 22 patients with heart failure (EF≤40%) had MRI brain and MRA. Lacunar infarction was present in three patients (18.75%); partial anterior circulation infarction was diagnosed in ten patients (62.5%), posterior circulation infarction in one patient (6.25%) and total anterior circulation infarction in two patients (12.5%) (Table 3 and Figure 1). Leucoaraiosis was present in 14 (87.5%) patients compared to 111 (75 %)patients for the whole sample and significant intracranial vessel stenosis in 14 (87.5%) patients compared to 117 (79.1%) patients for the whole sample; tables 2 and 3. In patients with HF, median NIHSS score at admission was 10.5 compared to 8 for the whole sample and at 1 month follow-up it was 5 compared to 4 for the whole sample (Tables 1 and 3). At follow-up, five patients (22.7%) of these patients died compared to 26 (13%) patients for the whole sample (Tables 1 and 3).

                There was no significant difference between cases with EF of >40 and those with EF of ≤ 40% as regards the level of NIHSS score at admission and at follow up P>0.05. However, cases with EF of ≤ 40% showed higher NIHSS score at admission than those without systolic dysfunction (EF>40%) but the difference did not reach a significant level P=0.09 (Table 4).

Diastolic dysfunction was present in 126patients (patients not in AF and had MRI brain and MRA).  Forty-three (87.8%) patients with lacunar infarcts had DD, while DD was present in 43 (89.4%) of those with partial anterior circulation infarction, 21 (91.4%) of those with posterior circulation infarction and in six patients (100%) of those with total anterior circulation infarction; table five. Differences were not statistically significant.

Patients with diastolic dysfunction had median NIHSS score of 7 with IQR of 4.00-11.50 at admission and 4 with IQR of 2.00-7.00 after one month and those without had a median NIHSS score of 7.5 with IQR of 5.50-12.00 at admission and 6 with IQR of 4.00-8.00 after one month (Table 6). There was no significant difference between  cases without  and those with diastolic dysfunction as regards the level of NIH at admission and at follow up P>0.05. However patients with diastolic dysfunction showed lower NIHSS score at follow up than patients without, but the difference did not reach a significant level P=0.07.

 

 


Table 1. Clinical patient’s characteristics and demographic data.

 

Variables

Number of patients

Frequency %

Age ( Mean±SD)

61.87±12.65

 

Sex:

        

Male

Female

118

82

59

41

Risk factors:

Hypertension

Cigarette smoking

Hypercholesterolemia

Diabetes mellitus

Ischemic heart disease

Atrial fibrillation

142

66

76

106

74

33

71

33

38

53

37

16.5

Clinical data:

 

NIHSS on admission*

NIHSS after 1 month*

8

4

5-14

2-8

Out come after 1 month

          

Alive

Dead

174

26

87

13

NIHSS National Institute of Health Stroke Scale,

*: data express as median

 

Table 2. Imaging characteristics of the patients.

 

Variables

Number of positive patients

Frequency %

Echocardiography : (n= 200)

Atrial fibrillation

DD in non AF patients

SWMA

LVH

Ejection fraction ≤ 40 %

           Left atrium > 40mm

 

33

147

61

106

22

113

 

16.5

88

30.5

53

11

56.5

Significant carotid stenosis (n= 200)

22

11

Types of CVS  by MRI(n= 148)

Lacunar

PACI

POCI

TACI

 

51

65

25

7

 

34.5

43.9

16.9

4.7

Leukoaraiosis (n= 148)

111

75

MRA  showing significant stenosis (n= 148)

117

79.1

CVS cerebrovascular disease, DD diastolic dysfunction, LVH left ventricular hypertrophy, MRA: Magnetic resonance Angiography, MRI: Magnetic resonance imaging, PACI: partial anterior circulation syndrome, POCI: posterior circulation infarction, SWMA Segmental wall motion abnormality, TACI: total anterior circulation infarction,

 

Table 3. Clinical and Radiological Data of Patients with Systolic Dysfunction.

 

 

 

n

%

p-value

Significance

Types (n=16)

Lacunar

3

18.75

0.07

NS

PACI

10

62.5

POCI

1

6.25

TACI

2

12.5

Leucoaraiosis(n=16)

Positive

14

87.5

0.28

NS

Negative

2

12.5

Significant carotid

stenosis(n=22)

Positive

0

0

0.09

NS

Negative

22

100

Significant intracranial

stenosis(n=16)

Positive

14

87.5

0.45

NS

Negative

2

12.5

NIHSS at admission (n=22)

10.5(IQR 5-21)

0.02

S

NIHSS at follow-up(n=17)

5(IQR 2.5-10.5)

Outcome (n=22)

Alive

17

 

Dead

5








NIHSS National institute of health stroke scale, NS non-significant, PACI partial anterior circulation infarction, POCI posterior circulation infarction, S significant, TACI total anterior circulation infarction

 

 

Figure 1. (A) Representative MRI brain diffusion weighted image of 55 years old female showing acute infarction in left frontotemporal regions and (B) magnetic resonance angiographic (MRA) image of the same patient showing significant severe left middle cerebral arteries (MCA) stenosis with absent distal flow (arrows).

               

Table 4. NIHSS at admission and follow-up in patients with and without systolic dysfunction.

 

 

Ejection fraction

P-value

≤40% (22)

>40% (178)

Median

IQR

Median

IQR

NIHSS   at admission

10.50

5.00-21.00

8.00

4.75-13.25

0.09

NS

NIHSS at follow-up

5.00

2.50-10.50

4.00

2.00-8.00

0.26

NS

IQR interquartile range, NIHSS National institute of health stroke scale, NS non-significant

 

Table 5. Diastolic dysfunction among different stroke types.

 

 

 

DD (in 126  non-AF patients who had an MRI)

P-value

Negative (13)

Positive (113)

n

%

n

%

Types

Lacunar

6

12.2%

43

87.8%

0.19

NS

PACI

5

10.4%

43

89.6%

0.13

NS

POCI

2

8.6%

21

91.4%

0.19

NS

TACI

0

0%

6

100%

0.45

NS

DD diastolic dysfunction, NS non-significant, PACI partial anterior circulation infarction, POCI posterior circulation infarction, TACI total anterior circulation infarction

 

Table 6. NIHSS at admission and follow-up in patients with and without diastolic dysfunction.

 

 

DD (167 patient not in AF)

P-value

Absent (20)

Present (147)

Median

IQR

Median

IQR

NIH at admission

7.50

5.50-12.00

7.00

4.00-11.50

0.26

NS

NIH at follow-up

6.00

4.00-8.00

4.00

2.00-7.00

0.07

NS

DD diastolic dysfunction, IQR interquartile range, NIHSS National institute of health stroke scale, NS non-significant.

 

 


DISCUSSION

 

Stroke is a major public health problem because it is frequent, dangerous and expensive. Moreover, it can often be prevented, and may be treatable in the acute stage. Stroke is associated with increased long-term mortality, residual physical, cognitive, and behavioral impairments, recurrence, and increased risk of other types of vascular event, such as myocardial infarction.7Heart failure is a major healthcare burden and is increasing in incidence and prevalence.8Despite efforts with various pharmacological interventions, mortality and morbidity remain high in patients with this common condition.HF is a common cause of ischemic stroke9,10, and several pathophysiologic mechanisms have been described.Previous  cohort data suggest that the risk of stroke and thromboembolism is greatest in the initial period (<30 days) following the diagnosis of HF, although the risk may still be evident until 6 months.11Indeed, postmortem studies suggest that many sudden deaths in HF have an etiology related to thromboembolism.12

                In our study, there was no statistically significant profile for patients with heart failure. However, these patients tended to have partial anterior circulation infarction (62.5%) which can be explained by the physiological fact that 80% of the blood ejected from the heart goes on directly into the carotid system and hence providing the rational why cardiac emboli tend to lodge in carotid system.7The most frequently recognized reasons for cardio embolic stroke in patients with  HF are thrombus formation due to  left ventricular (LV) hypokinesia.13,14 As a consequence of the activation of the sympathetic nervous system and of the renin-angiotensin-aldosterone system, there is a hypercoagulable state, increased aggregation of thrombocytes, and reduced fibrinolysis in patients with HF.15,16 Moreover, there is evidence of endothelial dysfunction in HF patients  and malfunctioning of cerebral autoregulation.17

                This group of patients also tended to show the fingerprints of ischemia represented by leucoaraiosis, which was present in 87.5%. However, drawing association was not possible as these patients had high incidence of intracranial vessel stenosis, which is known to cause these ischemic changes of the brain. These patients tended to have significant intracranial vessel stenosis (87.5% of patients compared to 79.1% for the whole sample) as noted above.In addition to the causal relation between HF and ischemic stroke, both entities represent manifestations of similar underlying risk factors, such as hypertension and diabetes mellitus.18Therefore, patients with HF are at risk for stroke of large-artery atherosclerosis as well as small-vessel occlusion.

                Heart failure patients also tended to score higher on the NIHSS (10.5 compared to 8 for the whole group at admission and 5 compared to 4 for the whole group at follow up) and to have higher mortality rate during the short term follow-up period of our study, 5 out of 22 patients (22.7%) compared to the whole study group (13%). This is concordant with previous study by Pullicino and his colleagues13who found that HF with impaired systolic function was associated with severer stroke and increased incidence of long-term mortality and morbidity after ischemic stroke. Also, Allison and his colleagues19, reported steady association between ischemic stroke and heart failure of variable severity.

                Diastolic dysfunction is a term applied clinically to patients presenting with symptoms of heart failure but found to have normal ejection fraction on echocardiography (>40%) and reversed E/A (Early passive flow/ flow under later Atrial contraction) ratio on Doppler study of mitral valve during routine echocardiography. This group constitutes about 50% of all patients diagnosed clinically with heart failure and has its own implications on treatment of heart failure symptoms as for example; vasodilators are avoided, as high ventricular filling pressure is needed.3No previous studies were yet done to assess its association with ischemic stroke.

                Interestingly, 88% of our patients without AF had DD, which is a high percentage. However, stroke severity was not higher in these patients but there were tendency of these patients to score lower on NIHSS during follow-up, and it was not possible to determine whether it is an independent risk factor for ischemic stroke due to the high prevalence of hypertension among the study group known to cause DD and thus making the association blurred.

                Limitations in our study included the small number of patients having heart failure. Other limitations included grouping of patients in categories of heart failure versus not heart failure rather than sub classifying them as mild, moderate or severe but number of patients was too small.

                Patients might have to be followed up for more prolonged periods to monitor for stroke recurrence as during the first month follow-up period, patients were hospitalized for variable periods during which many of them were anti-coagulated or received more than one antiplatelet drug  when patients for example had ischemic heart disease. Also during in-patient period, cardiac conditions were meticulously monitored and treated; sometimes by drugs given by continuous infusion such as dobutamine for heart failure and amiodarone for paroxysmal atrial fibrillation. Many of them were kept in the first few months following their cerebral ischemic event on these drugs or combinations of drugs, which may have by themselves impacted the stroke prognosis.

Conclusion

Heart failure tends to have a negative impact on the severity and prognosis of ischemic stroke patients. This may call for more meticulous examination and investigation of the cardiac patients by transthoracic or transesophageal echocardiography, stress echocardiography, stress ECG or thallium scanning according to individual patient and optimal management of their cardiac status besides intensive primary and secondary prevention strategies represented at this time for example by preferential use of drugs known to have anti-failure effects.

 

[Disclosure: Authors report no conflict of interest]

 

REFERENCES

 

1.          José B, Betsy B, Michael J. Vascular diseases of the nervous system. In: Bradley WG, Daroff RB, Fenichel G, Jankovic J, editors. Neurology in clinical practice.5th ed. Oxford: Butterworth-Heinemann; 2008. 1165-90p.

2.          Jacobsen SJ, Gersh BJ, Kottke TE, McCann HA, Bailey KR, Ballard DJ. The incidence and prevalence of congestive heart failure in Rochester, Minnesota. Mayo Clin Proc. 1993 ;68:1143-50.

3.          Camm AJ, Bunce N. Cardiovascular diseases.  In: Kumar P, Clark’s M, editors Kumar and Clark’s clinical medicine. 7th ed. Philadelphia: Saunders; 2009.p. 811-88.

4.          Hatano S. Experience from a multicenter stroke register: a preliminary report. Bull World Health Organ. 1976; 54:541-53.

5.          Lee LJ, Kidwell CS, Alger J, Saver L.  Impact on Stroke Subtype Diagnosis of Early Diffusion-Weighted Magnetic Resonance Imaging and Magnetic Resonance Angiography. Stroke. 2000; 31:1081-9.

6.          Samuels OB, Joseph GJ, Lynn MJ, Smith HA, Chimowitz MI. A standardized method for measuring intracranial arterial stenosis. AJNR Am J Neuroradiol.2000; 21:643-6.

7.          Cordonnier C, Leys D. Stroke, the bare essentials. Prac Neurol.  2008;8 :263-72.

8.          Bui AL, Horwich TB, Fonarow GC. Epidemiology and risk profile of heart failure. Nat Rev Cardiol. 2011;8:30-41.

9.          Lloyd-Jones D. Heart disease and stroke statistics-2010 update. Circulation. 2010;121:e46-e215.

10.       Hausler KG, Laufs U, Endres M. [Neurological aspects of chronic heart failure]. Nervenarzt. 2011;82:733-42. In German.

11.       Alberts VP, Bos MJ, Koudstaal PJ, Hofman A, Wettiman ACM, Stricker BHC, et al. Heart failure and the risk of stroke: the Rotterdam Study. Eur J Epidemiol. 2010;25:807-12.

12.       Uretsky BF, Thygesen K, Armstrong PW, Cleland JG, Horowitz JD, Massie BM, et al. Acute coronary findings at autopsy in heart failure patients with sudden death: results from the assessment of treatment with lisinopril and survival (ATLAS) trial. Circulation. 2000;102:611-6.

13.       Pullicino PM, Halperin JL, Thompson JL. Stroke in patients with heart failure and reduced left ventricular ejection fraction. Neurology.2000; 54:288-94.

14.       Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation is an independent risk factor for stroke: the Framingham Study. Stroke. 1991;22:983-8.

15.       Caldwell JC, Mamas MA, Neyses L, Garratt CJ. What are the thromboembolic risks of heart failure combined with chronic or paroxysmal AF? J Card Fail. 2010; 16:340-7.

16.       Jug B, Vene N, Salobir BG, Sebestjen M, Sabovic M, Keber I. Procoagulant state in heart failure with preserved left ventricular ejection fraction. Int Heart J. 2009;50:591-600.

17.       Georgiadis D, Sievert M, Cencetti S, Uhlmann F, Krivokuca M, Zierz S, et al. Cerebrovascular reactivity is impaired in patients with cardiac failure. Eur Heart J. 2000;21:407-13.

18.       Freudenberger RS, Hellkamp AS, Halperin JL, Poole J, Anderson J, Johnson G, et al. Risk factors for thromboembolism in the SCD-Heft Study. Circulation. 2007;115:2637-41.

19.       Allison G, Ralph L, Tanja R, Robert R, Zhezhen J, Rui. Left Ventricular Systolic Dysfunction and the Risk of Ischemic Stroke in a Multiethnic Population. Stroke. 2006;37;1715-9.


 

                               

 

 

 

 

 

 

 

 

 

الملخص العربي

 

أثر فشل عضله القلب على حده الجلطة الدماغية والتنبؤ بمآل المرض على المدى القريب: دراسة مصرية

 

يعد فشل عضله القلب من الأسباب المؤدية إلى حده الجلطة الدماغية والى زيادة معدل الوفاة على المدى البعيد.

الهدف من الدراسة: دراسة مدى تأثير بعض الاختلالات التركيبية او الوظيفية في عضله القلب على حدة ومأل الجلطة الدماغية وما إذا كانت تؤدى لنوع معين من الجلطات وفقاً لتقسيم مقاطعه اوكسفورد المعدل للسكتات الدماغية.

طريقه دراسة البحث: تمت هذه الدراسة على مائتين مريضا ممن يعانون من الجلطة الدماغية الحادة فى وحده السكتة الدماغية بمستشفى عين شمس التخصصي. وقد خضع كل المرضى إلى بيان تاريخ تفصيلي للمرض مع فحص سريري كاملو اعاده الفحص الإكلينيكي بعد مرور شهر، بالإضافة إلى فحص القلب بالموجات الصوتية. وقد خضع كل المرضى أيضا الى فحص دقيق بالرنين المغناطيسي للمخ والشرايين المخيه.

النتائج المستخلصة: تصل نسبه فشل عضله القلب إلى 11% من مرضى الجلطة الدماغية. 62.5% من هؤلاء المرضى مصابون باحتشاء جزئي للدورة الدموية الدماغية الأمامية. و 87.5% مصابون بتلف المادة البيضاء. وتصل معدلات ضيق الشرايين المخيه فى مرضى فشل عضله القلب الى87.5 % بالمقارنة ل 79% فى المجموعة كلها. وبالرغم من ان نتائج الدراسة لم تصل إحصائيا للحد المطلوب إلا أن مرضى قصور القلب كانت حده السكتة الدماغية لديهم أكثر من بقية مرضى الدراسة عند دخول المستشفى وأثناء المتابعة بعد شهر.



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