Carotid artery stenosis as an independent risk factor for perioperative strokes following mitral valve surgical intervention

Journal of the Neurological Sciences 382 (2017) 170–184

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Carotid artery stenosis as an independent risk factor for perioperative strokes following mitral valve surgical intervention

MARK

Reshmi Udesha, Pawan Solankia, Amol Mehtaa, Thomas Gleasonc, Lawrence Wechslerb, Parthasarathy D. Thirumalaa,b,⁎ a b c

Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA Department of Cardiothoracic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

A R T I C L E I N F O

A B S T R A C T

Keywords: Perioperative stroke Mitral valve surgery Carotid stenosis Mitral valve repair Mitral valve replacement

Objective: To examine the role of carotid stenosis (CS) and other independent risk factors of perioperative stroke following either mitral valve repair or replacement. Methods: Using data from the National Inpatient Sample (NIS) database for analysis, all patients who underwent either mitral valve repair or replacement were identified using ICD-9 codes. Results: A total of 79,583 patients who underwent either mitral valve replacement or repair were studied. 3.39% of the total cohort developed perioperative stroke. With a mean age of 62.78 ± 0.23, there was a statistically significant amount of stroke cases in age ranges 65–74 and 75–84 (p < 0.05). Risk stratification was done using Van Walraven (VWR) scoring and the cohort had a mean of 2.73 ± 0.06. The following independent predictors were found to be significant: age, female gender, moderate and high VWR risk, both symptomatic and asymptomatic CS, atrial fibrillation, previous h/o smoking, and other cardiac valve procedures performed, and congestive heart failure (CHF). Conclusion: CS is a significant risk factor for perioperative strokes following mitral valve surgery. Further prospective clinical studies are needed that look into risk stratification of patients for better patient selection and the question of whether carotid revascularization procedures will be beneficial in reducing stroke rates.

1. Introduction Perioperative strokes are a feared complication secondary to mitral valve surgical intervention with a high incidence rate of 8–10% and are a dominant cause for post-operative morbidity and quality of life [1–4]. Over 10,000 mitral valve (MV) procedures are performed each year in the US [5]with the number of procedures increasing annually due to a growing elderly population as well as a better understanding of valvular assessment, exposure, and repair [5–7]. An operative mortality of 2% for MV repair and 6% for MV replacement has been reported with mortality rates increasing depending on the complexity of the intervention [5]. Perioperative strokes secondary to emboli and hypoperfusion has been shown to be the strongest risk factor for post-operative morbidity and mortality following cardiac valve procedures including MV surgery [3,4,8,9]. A detailed analysis of the risk factors contributing to perioperative strokes on a large patient cohort will help us move forward in strategies to prevent them and thereby improve overall post-operative survival following MV surgery.

⁎

Symptomatic carotid stenosis appears to be a significant risk factor for the incidence of perioperative strokes following cardiac operations [1,4,9–11]. Previous studies show that the prophylactic treatment of carotid stenosis by carotid revascularization leads to lower mortality rates following coronary artery bypass and other cardiovascular procedures [10,11]. Extracorporeal pump systems house internal surfaces with foreign materials that promote the formation of gaseous or particulate microemboli despite heparinization, and cannulation and clamping/unclamping of the aorta elicits embolic showers, which increases the risk of ischemia during surgery [12]. Additionally, impaired cerebral autoregulation distal to the stenotic carotid artery further increases the risk of stroke in patients with comorbid diseases such as hypertension and diabetes [4,12–14].Vertebral and basilar artery stenoses have been reported to contribute to ischemic strokes following cardiac procedures [15]. Our primary aim of this study is to see if carotid artery stenosis is an independent risk factor for perioperative stroke secondary to mitral

Corresponding author at: Center for Clinical Neurophysiology, Department of Neurological Surgery, UPMC Presbyterian-Suite B-400, 200 Lothrop Street, Pittsburgh, PA 15213, USA. E-mail address: [email protected] (P.D. Thirumala).

http://dx.doi.org/10.1016/j.jns.2017.10.004 Received 7 March 2017; Received in revised form 4 September 2017; Accepted 4 October 2017 Available online 06 October 2017 0022-510X/ © 2017 Elsevier B.V. All rights reserved.

Journal of the Neurological Sciences 382 (2017) 170–184

R. Udesh et al.

Table 1 Baseline characteristics and perioperative stroke univariate analysis in patients undergoing either mitral valve replacement or mitral valve repair. Variables

Age - M ± SD < 65 65–74 75–84 > 85 Gender Male Female Race/ethnicity White African American Hispanic Asian Native American Other/missing Admission status Emergent Urgent Elective Risk Category Average von Walraven score Low risk (VWR < 5) Moderate risk (VWR 5–14) High risk (VWR > 14) Outcome Perioperative stroke Pre-operative risk factors Asymptomatic carotid stenosis Symptomatic carotid stenosis Asymptomatic + symptomatic carotid stenosis Precerebral artery stenosis (other) Cerebral occlusion Vertebral artery stenosis Basilar artery stenosis Congestive heart failure (CHF)/Left ventricular dysfunction Atrial fibrillation Previous h/o stroke or transient ischemic attack Infective endocarditis Aortic stenosis Previous h/o smoking Previous h/o MI and angina Previous h/o cardiac surgery Other cardiac valve procedures performed Previous h/o coronary artery disease w/CABG Cardiopulmonary bypass Elixhauser comorbidities CHF Multivalvular disease Pulmonary circulation disorders Peripheral vascular disease Paralysis Other neurological disorders Chronic pulmonary disorders DM, uncomplicated DM, complicated Hypothyroidism Renal failure Liver failure Peptic ulcer disease AIDS Lymphoma Metastatic cancer Solid tumor w/o metastasis Collagen vascular disorders Coagulopathy Obesity Weight loss

% of Patients

Perioperative strokes Yes % (n)

No %(n)

Unadjusted odds ratio (95% confidence interval CI)

p-Value

62.78 ± 0.23 47.53% 28.45% 22.70% 13.08%

2.84% 3.65% 4.14% 3.56%

97.16% 96.35% 95.86% 96.44%

(36,589) (21,737) (17,220) (994)

NA 1.296 (1.178–1.426) 1.478 (1.342–1.627) 1.263 (0.907–1.759)

NA < 0.001 < 0.001 0.167

50.11% 49.89%

2.98% (1188) 3.80% (1511)

97.02% (38,779) 96.20% (38,290)

NA 1.288 (1.189–1.394)

NA < 0.001

78.25% 8.58% 6.62% 2.70% 0.50% 3.34%

3.40% 3.81% 3.52% 3.48% 3.37% 3.49%

96.60% 96.19% 96,48% 96.52% 96.63% 96.51%

NA 1.123 1.036 1.023 0.990 1.027

NA 0.148 0.7 0.864 0.975 0.823

18.38% 19.36% 62.22%

5.59% (728) 4.14% (572) 2.52% (1113)

94.41% (12,326) 95.86% (13,294) 97.48% (43,117)

NA 0.729 (0.636–0.836) 0.436 (0.388–0.491)

NA < 0.001 < 0.001

2.73 ± 0.06 70.19% 27.62% 2.19%

2.15% (1198) 5.65% (1246) 14.43% (254)

97.85% (54,782) 94.35% (20,813) 85.57% (1493)

NA 0.729 (0.636–0.836) 0.436 (0.387–0.490)

NA < 0.001 < 0.001

1.21% 0.04% 1.24% 0.44% 0.15% 0.01% 0.00% 8.08%

5.08% (48) 50.02% (15) 6.44% (63) 4.05% (14) 10.29% (12) 0.00% (0) 0.00% (0) 3.04% (197)

94.02% (927) 48.98% (15) 93.56% (942) 95.95% (340) 89.71% (105) 100% (9) 100% (2) 96.96% (6286)

1.535 (1.151–2.047) 28.704 (13.965–58.999) 1.987 (1.543–2.559) 1.203 (0.6899–2.099) 3.283 (1.828–5.897) NA NA 0.885 (0.760–1.032)

0.004 < 0.001 < 0.001 0.514 < 0.001 NA NA 0.119

51.61% 13.66% 4.55% 1.63% 9.50% 39.70% 0.88% 0.78% 0.01% 88.76%

3.13% (1288) 2.53% (28) 16.42% (597) 3.66% (48) 1.95% (146) 3.18% (1009) 1.13% (8) 0.65% (4) 0.00% (0) 3.31% (2342)

96.87% (39,872) 97.47% (1070) 83.58% (3030) 96.34% (1244) 98.05% (7403) 96.82% (30,758) 98.87% (693) 99.35% (620) 100% (8) 96.69% (68,446)

0.0.852 (0.789–0.920) 0.738 (0.0.505–1.079) 6.905 (6.208–7.681) 1.085 (0.824–1.431) 0.541 (0.456–0.643) 0.900 (0.831–0.976) 0.324 (0.161–0.649) 0.185 (0.081–0.421) NA 0.826 (0.737–0.926)

< 0.001 0.117 < 0.001 0.56 < 0.001 0.011 0.001 < 0.001 NA 0.001

1.53% 1.29% 0.42% 5.59% 1.12% 2.71% 18.62% 13.31% 2.28% 7.86% 8.67% 1.13% 0.44% 0.10% 0.49% 0.12% 1.97% 1.97% 16.20% 5.65% 3.05%

12.68% (152) 13.21% (134) 12.37% (42) 5.20% (235) 54.05% (487) 17.57% (382) 2.90% (431) 3.16% (339) 5.42% (98) 2.28% (141) 5.38% (375) 3.97% (36) 4.03% (14) 2.43% (2) 3.04% (12) 3.13% (3) 2.72% (42) 2.59% (40) 4.20% (546) 2.61% (119) 10.29% (250)

87.32% 86.79% 87.63% 94.80% 45.95% 82.43% 97.10% 96.84% 94.58% 97.72% 94.62% 96.03% 95.97% 97.57% 96.96% 96.87% 97.28% 97.41% 95.80% 97.39% 89.71%

4.332 (3.625–5.177) 4.517 (3.743–5.450) 4.074 (2.856–5.812) 1.617 (1.378–1.896) 40.662 (34.879–47.404) 6.914 (6.170–7.748) 0.822 (0.734–0.921) 0.922 (0.812–1.047) 1.659 (1.314–2.095) 0.648 (0.551–0.762) 1.722 (1.537–1.929) 1.183 (0.813–1.721) 1.200 (0.724–1.988) 0.711 (0.184–2.743) 0.893 (0.486–1.642) 0.922 (0.292–2.906) 0.795 (0.587–1.076) 0.753 (0.558–1.017) 1.313 (1.182–1.459) 0.754 (0.617–0.923) 3.502 (3.016–4.066)

(1069) (821) (742) (36)

(1625) (200) (143) (56) (10) (72)

(46,186) (5105) (3937) (1590) (287) (1960)

(0.960–1.313) (0.865–1.241) (0.783–1.338) (0.530–1.848) (0.813–1.298)

3.39%

171

(1044) (880) (289) (4226) (413) (1784) (14,471) (10,312) (1713) (6127) (6567) (861) (337) (75) (374) (94) (1522) (1534) (12,403) (4403) (2179)

< 0.001 < 0.001 < 0.001 < 0.001 < 0.001 < 0.001 0.001 0.209 < 0.001 < 0.001 < 0.001 0.38 0.48 0.621 0.716 0.89 0.138 0.065 < 0.001 0.006 < 0.001 (continued on next page)

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R. Udesh et al.

Table 1 (continued) Variables

Fluid and electrolyte disorders Chronic blood loss anemia Nutritional anemia Alcohol abuse Drug abuse Psychoses Depression Hypertension

% of Patients

21.11% 1.23% 13.16% 1.57% 1.14% 1.29% 4.03% 43.50%

Perioperative strokes Yes % (n)

No %(n)

Unadjusted odds ratio (95% confidence interval CI)

p-Value

4.50% 4.09% 2.93% 4.09% 6.25% 2.91% 2.98% 2.73%

95.50% 95.91% 97.07% 95.91% 93.75% 97.09% 97.02% 97.27%

1.476 1.221 0.844 NA 1.920 0.853 0.873 0.694

< 0.001 0.227 0.007 NA < 0.001 0.362 0.172 < 0.001

(758) (40) (309) (53) (58) (30) (94) (950)

(16,104) (937) (10,200) (1205) (855) (994) (3118) (33,757)

(1.329–1.639) (0.883–1.688) (0.746–0.955) (1.459–2.526) (0.605–1.201) (0.719–1.061) (0.636–0.756)

MI- Myocardial infarction; NA- Not available; AIDS- Acquired immunodeficiency syndrome; CABG- Coronary artery bypass grafting.

2.1. Statistical analysis

valve surgery. Our secondary aim is to see if other extracranial and intracranial cerebral arterial stenosis are risk factors for perioperative stroke following MV surgery. We will also evaluate trends in perioperative stroke, and the relationship with carotid stenosis over time. Patients with carotid stenosis that has been symptomatic within the previous 6 months benefit from carotid revascularization before undergoing cardiac or major vascular surgery [16]. This study can help to clarify the viability of prophylactic carotid endarterectomy prior to mitral valve surgery. Further, we can also use intraoperative neurophysiological monitoring to detect hypoperfusion related to the carotid artery and other relevant biomarkers during the procedure [17].Outcomes of this study can help guide the future practice of preventative screening of carotid stenosis and the intense medical management that can be used pre- and post-operatively to reduce mortality [18,19].

The initial data extraction was done using SAS version 9.3 (SAS Institute, Inc., Cary, NC). The Hospital Weight Files provided by the NIS was merged into each individual year's dataset to ensure each hospital was accounted for at least once. We then combined each individual year into an aggregated database. The Elixhauser comorbidity index was created using the “Comorbidity Software” available at the HCUP website [20,22]. The van Walraven score was created using the van Walraven macro created by the Cleveland Clinic [23]. All subsequent analyses were performed using Stata version 14 (StataCorp, College Station, TX). Univariate analyses were done using the unpaired t-test for continuous variables and a survey-adjusted Wald test for all variables that were categorical in nature. 3. Results

2. Materials & methods

3.1. Baseline characteristics

Patients were selected from the National Inpatient Sample (NIS) database, which contains a patient population over the timespan of 11 years (1999–2011). Diagnoses and procedures were identified in this patient database using The International Classification of Diseases, Ninth Revision-Clinical Modification (ICD-9) codes (see Supplemental Table 1). 31 relevant ICD-9 Elixhauser comorbidities were used from the NIS Database [20,21].Pre- and post-operative patient baseline medical conditions all factor into the occurrence of perioperative stroke for patients undergoing mitral valve surgery and were taken into account as a covariate if not already a part of an Elixhauser diagnosis group. Preoperative (patient-related) risk factors include: advanced age (> 70 yrs), female sex, history of hypertension, history of emboli, diabetes mellitus, renal insufficiency (creatinine, > 2 mg/dl [177 μmol/l]), smoking, chronic obstructive pulmonary disease, peripheral vascular disease, cardiac disease (coronary artery disease, arrhythmias, heart failure), systolic dysfunction (ejection fraction, < 40%), history of stroke or transient ischemic attack, carotid stenosis (especially if symptomatic), atherosclerosis of the ascending aorta, and abrupt discontinuation of antithrombotic therapy before surgery [6,9]. Intraoperative (procedure-related) risk factors include the complexity of the cardiac surgical intervention, type of anesthesia (general or local), and cardiac bypass time (> 2 h) [1,9]. Postoperative risk factors include heart failure, low ejection fraction, myocardial infarction, or arrhythmias (atrial fibrillation), dehydration/blood loss, and hyperglycemia [1,6,8,9]. Subgroup analyses were done for patients who underwent isolated mitral valve replacement (subgroup1) and mitral valve repair (subgroup2). The outcome studied was perioperative strokes.

A total of 79,583 patients who underwent either mitral valve replacement or repair were studied. 3.39% of the total cohort developed perioperative stroke. With a mean age of 62.78 ± 0.23, there was a statistically significant amount of stroke cases in age ranges 65–74 and 75–84 (p < 0.05). Females were found to be statistically more likely to develop perioperative strokes (p < 0.05). Risk stratification was done using Van Walraven (VWR) scoring and the cohort had a mean of 2.73 ± 0.06. See Table 1. 3.1.1. Subgroup 1 A total of 47,329 patients who underwent mitral valve replacement (MVR) were studied. 3.98% of the total cohort developed perioperative strokes. With a mean age of 64.01 ± 0.19, there was a statistically significant amount of stroke cases in the age range 75–84 (p < 0.05). Risk stratification using VWR had a mean of 2.97 ± 0.06. A higher risk category was correlated with a higher incidence of perioperative stroke (p < 0.05). See Table 2. 3.1.2. Subgroup 2 A total of 32,822 patients who underwent just mitral valve repair were studied. 2.56% of the total cohort developed perioperative strokes. With a mean age of 60.94 ± 0.35, there was a statistically significant amount of stroke cases in the in age ranges 65–74 and 75–84 (p < 0.05). Females were statistically more likely to develop perioperative stroke (p < 0.05). Risk stratification using VWR had a mean of 2.39 ± 0.07. A higher risk category was correlated with a higher incidence of perioperative stroke (p < 0.05). See Table 2.

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Table 2 Baseline characteristics and perioperative stroke univariate analysis in patients undergoing isolated mitral valve replacement (subgroup 1 - gray) and patients undergoing isolated mitral valve repair (subgroup 2 - white).

Variables

% of Patients

Perioperative Strokes Yes % (n)

No % (n)

Unadjusted Odds Ratio (95% CI) p-value

64.01±0.19 Age -M±SD

<65

65-74

75-84

>85

60.94± 0.35 44.80%

3.68% (776) 96.32% (20,303)

NA

NA

51.57%

1.81% (304) 98.19% (16,580)

NA

NA

29.33%

4.06% (558) 95.94% (13,241)

1.109 (0.990-1.243)

0.073

27.14%

3.03% (271)

96.97% (8,631)

1.700 (1.431-2.019)

<0.001

24.42%

4.42% (508) 95.58% (10,962)

1.211 (1.070-1.371)

0.002

20.18%

3.70% (242)

96.30% (6,362)

2.085 (1.758-2.474)

<0.001

1.45%

3.29% (22)

96.71% (656)

0.892 (0.595-1.337)

0.58

1.11%

3.98% (14)

96.02% (346)

2.252 (1.312-3.863)

0.003

44.06%

3.80% (793) 96.20% (20,110)

NA

NA

58.90%

2.12% (409) 97.88% (18,963)

NA

NA

Gender

Male

Female

55.94% 4.12% (1,093) 95.88% (25,418)

1.089 (0.996-1.192)

0.062

41.10%

3.19% (431) 96.81% (13,120)

1.152 (1.130-1.769)

<0.001

76.76% 4.08% (1,145) 95.92% (26,974)

NA

NA

Race/Ethnicity

White

80.48% 9.24%

African American

Hispanic

Asian

Native American Other/Missing

2.52% (504) 97.48% (19,537) 4.25% (144)

NA

NA

95.75% (3,265)

1.044 (0.873-1.249)

0.637

7.63%

2.94% (56)

97.06% (1,878)

1.171 (0.892-1.537)

0.256

7.38%

4.19% (114)

95.81% (2,613)

1.028 (0.838-1.262)

0.789

5.47%

2.15% (29)

97.85% (1,346)

0.847 (0.601-1.196)

0.346

2.73%

4.20% (41)

95.80% (956)

1.031 (0.761-1.395)

0.845

2.65%

2.35% (15)

97.65% (643)

0.931 (0.544-1.594)

0.795

0.43%

5.32%(8)

94.68% (145)

1.323 (0.708-2.474)

0.381

0.61%

1.34% (2)

98.66% (143)

0.524 (0.155-1.768)

0.297

3.46%

3.63% (46)

96.37% (1,212)

0.886 (0.669-1.173)

0.398

3.16%

3.34% (27)

96.66% (757)

1.337 (0.880-2.031)

0.173

Admission Status 20.60%

6.23% (540)

93.77% (8,160)

NA

NA

Emergent

15.15%

4.35% (193)

95.65% (4,245)

NA

NA

20.81%

4.56% (402)

95.44% (8,448)

0.719 (0.621-0.831)

<0.001

Urgent

17.27%

3.43% (175)

96.57% (4,934)

0.782 (0.608-1.006)

0.056

58.56%

2.95% (730) 97.05% (24,024)

0.457 (0.401-0.521)

<0.001

Elective

67.54%

2.02% (398) 97.98% (19,397)

0.453 (0.367-0.559)

<0.001

2.64% (853) 97.36% (31,520)

NA

NA NA <0.001

Risk Category Average von Walraven Score Low Risk (VWR<5) Moderate Risk (VWR 5-14) High Risk (VWR >14)

2.97±0.06 2.39±0.07 68.32% 72.76%

1.48% (353) 98.52% (23,620)

NA

29.04%

6.17% (852) 93.83% (12,933)

2.420 (2.193-2.671)

25.65%

4.92% (413)

95.08% (8,044)

3.436 (2.875-4.107)

2.63%

14.48% (180)

85.52% (1,067)

6.232 (5.188-7.485)

1.58%

13.76% (74)

86.24% (446)

10.600 (8.009-14.027)

<0.001 <0.001 <0.001

Outcome Perioperative Stroke

3.98%

173

2.56% (continued on next page)

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Table 2 (continued)

Preoperative Risk Factors Asymptomatic Carotid Stenosis Symptomatic Carotid Stenosis Asymptomatic + Symptomatic Carotid Stenosis Precerebral Artery Stenosis (other)

Cerebral Occlusion Vertebral Artery Stenosis Basilar Artery Stenosis Congestive Heart Failure (CHF)/LVD

Atrial Fibrillation Previous h/o Stroke or TIA

1.21%

4.74% (27)

95.26% (553)

1.204 (0.822-1.765)

1.21%

5.74% (22)

94.26% (380)

2.358 (1.514-3.672)

0.04%

44.81% (9)

55.19% (11)

19.676 (8.122-47.665)

0.34 <0.001 <0.001 <0.001

0.03%

60.45% (6)

39.55% (4)

58.637 (16.394-209.735)

1.25%

6.11% (36)

93.89% (564)

1.580 (1.129-2.210)

0.008

1.24%

7.09% (28)

92.91% (384)

2.976 (2.003-4.420)

<0.001

0.44%

4.43% (9)

95.57% (200)

1.118 (0.543-2.303)

0.762

0.46%

4.66% (7)

95.34% (146)

1.868 (0.883-3.953)

0.102

0.18%

8.30% (7)

91.70% (79)

2.187 (1.032-4.632)

0.041

0.09%

15.30% (5)

84.70% (27)

6.917 (2.654-18.026)

<0.001

0.01%

0.00% (0)

100.00% (3)

NA

NA

0.02%

0.00% (0)

100.00% (0)

NA

NA

0.00%

0.00% (0)

100.00% (2)

NA

NA

0.00%

0.00% (0)

0.00% (0)

NA

NA

10.95%

3.02% (158)

96.98% (5,058)

0.729 (0.615-0.863)

<0.001

3.94%

3.22% (42)

96.78% (1,271)

1.280 (0.920-1.782)

0.143

55.58%

3.37% (886) 96.63% (25,449)

0.700 (0.640-0.764)

<0.001

45.84%

2.75% (415) 97.25% (14,688)

1.152 (1.008-1.318)

0.038

97.05% (641)

0.730 (0.463-1.150)

0.175 0.375 <0.001

13.88%

2.95% (20)

13.25%

1.88% (8)

98.12% (434)

0.726 (0.357-1.475)

6.40%

16.59% (505)

83.41% (2,529)

6.179 (5.500-6.942)

1.91%

15.32% (96)

84.68% (534)

7.652 (6.018-9.731)

1.86%

3.73% (33)

96.27% (848)

0.932 (0.671-1.295)

0.675

Aortic Stenosis

1.32%

3.89% (17)

96.11% (410)

1.553 (0.931-2.592)

0.092

Previous h/o Smoking

8.76%

2.07% (86)

97.93% (4,072)

0.486 (0.392-0.602)

<0.001

10.43%

1.81% (61)

98.19% (3,373)

0.677 (0.515-0.890)

0.005

39.12%

3.42% (635) 96.58% (17,937)

0.779 (0.708-0.856)

<0.001

40.37%

2.87% (381) 97.13% (12,988)

Infective Endocarditis

Previous h/o MI and Angina Previous h/o Cardiac Surgery Other Cardiac Valve Procedures Performed Previous h/o Coronary Artery Disease w/ CABG Cardiopulmonary Bypass Previous h/o MI and Angina Previous h/o Cardiac Surgery Other Cardiac Valve Procedures Performed Previous h/o Coronary Artery Disease w/ CABG Cardiopulmonary Bypass

<0.001

1.227 (1.057-1.425)

0.007

0.81%

1.03% (4)

98.97% (377)

0.249 (0.091-0.682)

0.007

1.00%

1.21% (4)

98.79% (326)

0.463 (0.175-1.229)

0.122

0.64%

1.32% (4)

98.68% (301)

0.321 (0.143-0.717)

0.006

0.97%

0.00% (0)

100.00% (323)

NA

NA

0.01%

0.00% (0)

100.00% (6)

NA

NA

0.01%

0.00% (0)

100.00% (2)

NA

NA

87.73% 3.91% (1,626) 96.09% (39,936)

0.871 (0.763-0.994)

0.04

90.14%

2.48% (735) 97.52% (28,963)

0.759 (0.608-0.948)

0.015

40.37%

2.87% (381) 97.13% (12,988)

1.227 (1.057-1.425)

0.007

0.81%

1.03% (4)

98.97% (377)

0.249 (0.091-0.682)

0.007

1.00%

1.21% (4)

98.79% (326)

0.463 (0.175-1.229)

0.122

0.64%

1.32% (4)

98.68% (301)

0.321 (0.143-0.717)

0.006

0.97%

0.00% (0)

100.00% (323)

NA

NA

0.01%

0.00% (0)

100.00% (6)

NA

NA

0.01%

0.00% (0)

100.00% (2)

NA

NA

87.73% 3.91% (1,626) 96.09% (39,936)

0.871 (0.763-0.994)

0.04

0.759 (0.608-0.948)

0.015

90.14%

2.48% (735) 97.52% (28,963)

174

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Table 2 (continued)

Elixhauser Comorbidities 1.90% CHF Multivalvular Disease Pulmonary Circulation Disorder Peripheral Vascular Disease

Paralysis Other Neurological Disorders Chronic Pulmonary Disorders

13.51% (120)

86.49% (767)

3.958 (3.232-4.848)

1.02%

10.81% (35)

89.19% (288)

4.779 (3.303-6.915)

1.58%

14.38% (107)

85.62% (638)

4.238 (3.457-5.195)

0.86%

10.73% (30)

89.27% (249)

4.711 (3.254-6.818)

0.54%

13.71% (35)

86.29% (215)

3.885 (2.632-5.735)

0.26%

8.95% (8)

91.05% (77)

3.766 (1.777-7.980)

5.87%

5.87% (164)

94.13% (2,625)

1.551 (1.292-1.862)

5.15%

4.13% (73)

95.87% (1,624)

1.701 (1.283-2.254)

1.22%

52.08% (303)

47.92% (276)

31.025 (25.911-37.151)

1.00%

56.59% (188)

43.41% (146)

63.485 (49.288-81.771)

2.90%

17.91% (248)

82.09% (1,127)

5.905 (5.153-6.766)

2.44%

17.29% (139)

82.71% (667)

9.331 (7.552-11.529)

20.45%

3.04% (296)

96.96% (9,428)

0.711 (0.619-0.818)

<0.001 <0.001 <0.001 <0.001 <0.001 0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001

15.89%

2.60% (136)

97.40% (5,117)

1.020 (0.837-1.244)

0.842

13.92%

3.44% (230)

96.56% (6,374)

0.839 (0.720-0.977)

0.024

12.38%

2.68% (109)

97.32% (3,992)

1.056 (0.859-1.299)

0.605

2.46%

5.53% (64)

94.47% (1,095)

1.426 (1.092-1.862)

2.02%

5.48% (36)

94.52% (624)

2.263 (1.586-3.227)

0.009 <0.001

8.27%

2.49% (97)

97.51% (3,824)

0.593 (0.488-0.723)

Hypothyroidism

7.24%

1.97% (45)

98.03% (2,338)

0.780 (0.556-1.012)

9.61%

5.83% (267)

94.17% (4,309)

1.575 (1.381-1.796)

Renal Failure

7.33%

4.51% (110)

95.49% (2,308)

1.917 (1.559-2.358)

1.31%

4.32% (27)

95.68% (592)

1.090 (0.712-1.671)

0.691

0.87%

3.12% (9)

96.88% (277)

1.229 (0.636-2.375)

0.539

0.51%

3.84% (9)

96.16% (233)

0.962 (0.513-1.804)

0.904

0.34%

5.15% (6)

94.85% (106)

2.076 (0.960-4.490)

0.064

Diabetes Mellitus , Uncomplicated Diabetes Mellitus , Complicated

Liver Failure Peptic Ulcer Disease

<0.001 0.06 <0.001 <0.001

0.12%

1.73% (1)

98.27% (53)

0.425 (0.062-2.908)

0.383

AIDS

0.07%

3.95% (1)

96.05% (23)

1.565 (0.209-11.718)

0.663

Lymphoma

0.51%

2.83% (7)

97.17% (232)

0.703 (0.304-1.627)

0.41

0.45%

3.37% (5)

96.63% (142)

1.329 (0.552-3.199)

0.525

0.14%

3.15% (2)

96.85% (62)

0.785 (0.195-3.154)

0.773

Metastatic Cancer Solid Tumor w/o Metastasis Collagen Vascular Disorders

0.10%

3.09% (1)

96.91% (32)

1.216 (0.165-8.959)

0.848

2.21%

3.24% (33)

96.76% (1,007)

0.804 (0.571-1.133)

0.212

1.64%

1.82% (10)

98.18% (528)

0.702 (0.377-1.308)

0.265

2.27%

2.74% (29)

97.26% (1,047)

0.675 (0.468-0.972)

0.035

1.54%

2.22% (11)

97.78% (495)

0.861 (0.485-1.531)

0.611

16.83%

4.87% (390)

95.13% (7,605)

1.295 (1.148-1.460)

<0.001

Coagulopathy

15.45%

3.20% (164)

96.80% (4,928)

1.320 (1.103-1.581)

0.002

5.88%

3.13% (88)

96.87% (2,702)

0.769 (0.611-0.968)

0.026

Obesity

5.31%

1.75% (31)

98.25% (1,728)

0.664 (0.456-0.967)

3.68%

10.46% (182)

89.54% (1,562)

3.012 ( 2.529-3.588)

0.033 <0.001

2.15%

9.55% (68)

90.45% (639)

4.287 (3.253-5.648)

<0.001

Weight Loss Fluid and Electrolyte Disorders

21.76%

5.18% (536)

94.82% (9,795)

1.444 (1.283-1.625)

20.25%

3.43% (228)

96.57% (6,444)

1.485 (1.249-1.765)

Chronic Blood Loss Anemia

1.32%

4.95% (31)

95.05% (593)

1.260 (0.890-1.784)

0.192

1.09%

2.57% (9)

97.43% (348)

1.004 (0.504-2.001)

0.99

175

<0.001 <0.001

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Table 2 (continued)

13.50%

3.40% (220)

96.60% (6,192)

0.831 (0.721-0.957)

0.01

12.65%

2.18% (90)

97.82% (4,078)

0.830 (0.666-1.035)

0.098

1.55%

5.14% (39)

94.86% (701)

NA

NA

Alcohol Abuse

1.60%

2.58% (14)

97.42% (512)

NA

NA

1.35%

6.86% (45)

93.14% (592)

1.796 (1.318-2.446)

<0.001

Drug Abuse

0.85%

4.77% (13)

95.23% (266)

1.922 (1.088-3.396)

0.024

1.41%

2.83% (19)

97.17% (646)

0.699 (0.443-1.104)

0.124

1.13%

2.98% (11)

97.02% (358)

1.171 (0.652-2.103)

0.597

4.11%

3.48% (67)

96.52% (1,874)

0.864 (0.672-1.111)

0.255

2.20% (27)

0.381 <0.001

Nutritional Anemia

Psychoses

Depression

97.80% (1,264)

0.850 (0.592-1.221)

42.41%

3.91%

3.20% (645) 96.80% (19,445)

0.692 (0.626-0.765)

44.94%

2.10% (311) 97.90% (14,516)

0.710 (0.614-0.821)

<0.001 Hypertension

MI- Myocardial infarction; NA- Not available; AIDS- Acquired immunodeficiency syndrome; CABG- Coronary artery bypass grafting; CI-Confidence interval.

In subgroup1, patients the following independent predictors were found to be significant: age, female gender, moderate and high VWR risk, both symptomatic and asymptomatic CS, atrial fibrillation, previous h/o smoking, other cardiac valve procedures performed, and CHF. In subgroup2, patients the following independent predictors were found to be significant: age, female gender, moderate and high VWR risk, asymptomatic carotid stenosis, and previous h/o smoking. See Table 3.

3.2. Univariate predictors of in-hospital mortality and morbidity In patients who underwent either MVR or repair, the univariate preoperative risk factors included: asymptomatic/symptomatic CS, cerebral occlusion, atrial fibrillation, infective endocarditis, previous h/o smoking, previous h/o MI and angina, previous h/o cardiac surgery, other cardiac valve procedures performed, and cardiopulmonary bypass (p < 0.05). Statistically significant comorbidities included: CHF, multivalvular disease, pulmonary circulation disorders, peripheral vascular disorders, paralysis, other neurological disorders, chronic pulmonary disorders, complicated DM, hypothyroidism, renal failure, coagulopathy, weight loss, fluid and electrolyte disorders, drug abuse, and hypertension (p < 0.05). (Table 1).

3.4. Trend analysis (1999–2011) In patients who underwent mitral valve replacement and repair, perioperative stroke rates have remained relatively constant over the trend period (~ 2–5%), with a maximum percentage of reported cases reported in the year 1999, with 221 cases. Average age also remains relatively constant over time. Average VWR score and percentage of high-risk category has seen a positive trend over time. See Table 4. In subgroup 1, perioperative stroke rates have remained relatively constant over the trend period (~ 2–5%), With a maximum percentage of reported cases reported in the year 2010, with 175 cases. Average age also remains relatively constant over time. Average VWR score and percentage of high-risk category has a positive trend over time (Table 5). In subgroup2 perioperative stroke rates have remained relatively constant over the trend period (~ 2–3.5%), with a maximum percentage of reported cases reported in the year 2003, with 70 cases. Average age also remains relatively constant over time. Average VWR score and percentage of high-risk category displays a positive trend over time (Table 6).

3.2.1. Subgroup 1 & 2 In patients who underwent isolated mitral valve replacement and isolated mitral valve repair the following univariate pre-operative risk factors were found significant: symptomatic carotid stenosis, asymptomatic + symptomatic carotid stenosis, cerebral occlusion, CHF/LVD, atrial fibrillation, infective endocarditis, previous h/o smoking, previous h/o MI and angina, previous h/o cardiac surgery, other cardiac valve procedures performed, and cardiopulmonary bypass (p < 0.05). Statistically significant comorbidities included: CHF, multivalvular disease, pulmonary circulation disorders, peripheral vascular disease, paralysis, other neurological disorders, chronic pulmonary disorders, uncomplicated DM, complicated DM, hypothyroidism, renal failure, collagen vascular disorders, coagulopathy, obesity, weight loss, fluid and electrolyte disorders, nutritional anemia, drug abuse, and hypertension (p < 0.05) (Table 2).

4. Discussion 3.3. Independent predictors of perioperative stroke by multivariate analysis Our study evaluates the role of carotid stenosis (CS) and other independent risk factors of perioperative stroke following either mitral valve repair or replacement in 79,583 patients from NIS. The trend analysis reports a relatively constant perioperative stroke rate of 2–5% following mitral valve surgery (either MVR or mitral valve repair) over a period of ten years from 1999 to 2011. Despite advancements in surgical expertise and anesthetic techniques there have been no

In patients who underwent either mitral valve replacement and/or repair, infective endocarditis was the strongest independent predictor for perioperative stroke. Other independent predictors included: age, female gender, moderate and high VWR risk, both symptomatic and asymptomatic CS, atrial fibrillation, previous h/o smoking, other cardiac valve procedures performed, and CHF. See Table 3.

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Table 3 (continued)

Table 3 Multivariate logistic regression analysis- asymptomatic carotid stenosis.

Variables Variables

Age Female gender Risk category Moderate risk (VWR 5–14) High risk (VWR > 14) Perioperative risk factors Asymptomatic carotid stenosis Asymptomatic + symptomatic carotid stenosis Atrial fibrillation Infective endocarditis Previous h/o MI and angina Previous h/o smoking Other cardiac valve procedures performed Previous h/o coronary artery disease w/CABG Cardiopulmonary bypass

Odds ratio

95% C.I.

p-Value

1.016413 1.312291

(1.013234–1.019602) (1.20869–1.424772)

2.284268 4.733594

(2.072091–2.518173) (3.880937–5.773582)

< 0.001 < 0.001 < 0.001 < 0.001 < 0.001

1.416563

(1.037835–1.933495)

0.028

1.849824

(1.400434–2.443419)

< 0.001

0.8477337 6.226761 0.9688723 0.6488423 0.258874

(0.7818284–0.9191946) (5.536546–7.003023) (0.8879106–1.057216) (0.5466721–0.7701075) (0.1169269–0.5731422)

< 0.001 < 0.001 0.477 < 0.001 0.001

1

NA

NA

0.9543336

(0.8492276–1.072448)

0.432

Elixhauser comorbidities CHF Pulmonary circulation disorders

1.372422 1.055752

(1.084307–1.737093) (0.6817109–1.635021)

0.008 0.808

Variables

Mitral valve replacement Odds ratio

95% C.I.

p-Value

Age Female gender

1.014393 1.198819

(1.01065–1.018149) (1.091378–1.316838)

< 0.001 < 0.001

Risk category Moderate risk (VWR 5–14) High risk (VWR > 14)

2.020271 3.783855

(1.823358–2.238448) (3.004276–4.765728)

< 0.001 < 0.001 < 0.001

1.212127

(0.8044176–1.826479)

0.358

1.598164

(1.106878–2.307505)

0.012

0.7840016 5.47374 0.9005349 0.5979341 0.4489152

(0.714534–0.8602229) (4.827482–6.206512) (0.8141467–0.9960896) (0.4833789–0.7396375) (0.2062133–0.977264)

< 0.001 < 0.001 0.042 < 0.001 0.044

1

NA

NA

0.9911129

(0.8637123–1.137306)

0.899

1.399022 1.162355

(1.068414–1.831932) (0.7197253–1.877202)

0.015 0.538

Perioperative risk factors Asymptomatic carotid stenosis Asymptomatic + symptomatic carotid stenosis Atrial fibrillation Infective endocarditis Previous h/o MI and angina Previous h/o smoking Other cardiac valve procedures performed Previous h/o coronary artery disease w/CABG Cardiopulmonary bypass Elixhauser comorbidities CHF Pulmonary circulation disorders Variables

Mitral valve repair

Mitral valve replacement and repair

Asymptomatic + symptomatic carotid stenosis Atrial fibrillation Infective endocarditis Previous h/o MI and angina Previous h/o smoking Other cardiac valve procedures performed Previous h/o coronary artery disease w/CABG Cardiopulmonary bypass Elixhauser comorbidities CHF Pulmonary circulation disorders

95% C.I.

p-Value

Age Female gender

1.018429 1.452758

(1.011892–1.025007) (1.249165–1.689534)

< 0.001 < 0.001

Risk category Moderate risk (VWR 5–14) High risk (VWR > 14)

2.950619 7.060807

(2.467834–3.527851) (5.111186–9.754096)

< 0.001 < 0.001 < 0.001

Perioperative risk factors Asymptomatic carotid stenosis

1.841067

(1.1451–2.960029)

0.012

95% C.I.

p-Value

2.362882

(1.535392–3.636341)

< 0.001

0.9504535 7.288771 1.091635 0.7456858 1

(0.8242353–1.096) (5.635418–9.427196) (0.9307735–1.280297) (0.570321–0.9749725) NA

0.484 < 0.001 0.281 0.032 NA

1

NA

NA

0.8846968

(0.7162027–1.092831)

0.256

1.419914 0.8048709

(0.919624–2.192371) (0.3060665–2.116589)

0.114 0.66

MI- Myocardial infarction; NA- Not available; AIDS- Acquired immunodeficiency syndrome; CABG- Coronary artery bypass grafting; CI-Confidence interval.

significant reduction in stroke episodes and its associated morbidity and mortality [1]. This finding warrants further examination of risk factors and their association with perioperative strokes. Results of our study show age, female gender and higher VWR scores to be significant predictors of perioperative strokes following both mitral valve repair and replacement. The increased stroke risk with advancing age has been a well reported association attributed to the increased incidence of comorbid conditions such as diabetes, hypertension, cerebrovascular disease, coronary artery disease, etc. [24–26]. As with any cardiac procedure women have been shown to have a three-fold increased stroke risk post-procedure [4,26]. None of the ethnic groups analyzed had a significant association with perioperative stroke incidence following mitral valve procedures. Multivariate regression analysis shows asymptomatic and symptomatic carotid stenosis to be an independent predictor of perioperative stroke for both valve repair and MVR (OR 1.84(95% CI 1.40–2.44, p < 0.001). This finding gives impetus for pre-operative carotid Doppler screening in patients being considered for mitral valve procedures to aid in better patient selection. Its utility has been extensively studied prior to transcatheter aortic valve implantation [27] and coronary artery bypass grafting. However, its role in mitral valve procedures requires further workup. Further studies, which explore the efficacy of carotid revascularization prior to valve surgery, are required [28,29]. Several studies attribute carotid stenosis [1], vertebral [30]and basilar artery stenosis [31]to be predisposing factors for ischemic intraoperative strokes. However, our study coded very few patients were screened and diagnosed for vertebral and basilar artery stenosis and we were unable to study their association with perioperative strokes. Preventive strategies such intra-operative neuromonitoring with SSEP and EEG could be valuable adjuncts to help predict strokes [17,32].Postoperative care pathways with physical therapy and adequate medical management could help improve recovery rates following perioperative strokes. Atrial fibrillation and infective endocarditis were both significant independent predictors of perioperative strokes following mitral valve surgery with odds ratios of 0.84 (95% CI 0.78–0.91, p < 0.001) and 6.22 (5.53–7.01, p < 0.001) respectively. Atrial fibrillation and infective endocarditis have long been implicated in intra-operative and post-operative embolization with resultant neurological deficits [1,33–35]. Studies show infective endocarditis to be associated with a 12–40% stroke risk due to cerebral septic embolism without the added risk of valve surgery [36]. CHF was found to be another significant predictor of perioperative strokes with an OR of 1.37 (95% CI

Mitral valve repair Odds ratio

Odds ratio

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Table 4 Trend analysis over the years 1999–2011 for patients undergoing either mitral valve replacement or mitral valve repair. Calendar year

1999

2000

2001

POS % (n) Average age Perioperative stroke < 65 65–74 75–84 > 85

4.22 (221) 62.47349 No C.I. Yes % (n) 1.25% 1.49% 1.39% 0.04%

No % (n) 43.66% 29.42% 21.93% 0.82%

3.62 (204) 62.93082 No C.I. Yes % (n) 1.20% 1.28% 1.13% 0.04%

No % (n) 44.71% 30.05% 20.64% 0.96%

3.41 (203) 62.80791 (61.70941–63.90642) Yes % (n) 0.99% 1.33% 0.99% 0.07%

No % (n) 44.54% 29.02% 21.80% 1.26%

Gender Male Female

1.66% 2.56%

45.35% 50.43%

1.42% 2.20%

45.09% 51.29%

1.48% 1.94%

47.98% 48.60%

Risk category Average VWR score Low risk (VWR < 5) Moderate risk (VWR 5–14) High risk (VWR > 14)

1.940615 No C.I. 78.65% No C.I. 20.66% No C.I. 0.69% No C.I.

1.796111 No C.I. 80.63% No C.I. 18.84% No C.I. 0.53% No C.I.

1.977345 (1.807586–2.147104) 77.77% (75.79–79.63) 21.40% (19.68513–23.22533) 0.83% (0.59441–1.16748)

Calendar year

2002

2003

2004

POS % (n) Average age Perioperative stroke < 65 65–74 75–84 > 85

3.5 (211) 62.91362 (61.87661–63.95063) Yes % (n) 1.31% 1.02% 1.08% 0.04%

No % (n) 44.92% 27.51% 22.95% 1.18%

3.38 (228) 62.95865 No C.I. Yes % (n) 1.37% 0.91% 1.04% 0.03%

No % (n) 46.21% 27.07% 22.44% 0.94%

3.02 (178) 63.08602 (62.28511–63.88694) Yes % (n) 1.28% 0.99% 0.71% 0.02%

No % (n) 46.03% 26.00% 23.64% 1.34%

Gender Male Female

1.50% 1.99%

46.31% 50.20%

1.51% 1.88%

47.70% 48.92%

1.21% 1.82%

49.43% 47.55%

Risk category Average VWR score Low risk (VWR < 5) Moderate risk (VWR 5–14) High risk (VWR > 14)

2.106127 (1.962087–2.250167) 77.08% (75.34031–78.72668) 22.02% (20.40761–23.72645) 0.90% (0.6996–1.15814)

2.136177 No C.I. 76.14% NA 22.94% NA 0.91% NA

2.302201 (2.1258–2.478603) 74.36% (72.4927–76.14453) 24.34% (22.63331–26.12909) 1.30% (1.00512–1.68033)

Calendar year

2005

2006

2007

POS % (n) Average age Perioperative stroke < 65 65–74 75–84 > 85

3.04 (199) 61.47388 (59.97447–62.97328) Yes % (n) 1.34% 0.96% 0.68% 0.08%

No % (n) 46.84% 26.95% 22.02% 1.13%

2.62 (182) 62.53816 (61.29702–63.77929) Yes % (n) 1.05% 0.72% 0.82% 0.02%

No % (n) 47.99% 26.96% 21.20% 1.25%

2.84 (160) 63.18488 (62.3159–64.05386) Yes % (n) 0.99% 0.99% 0.81% 0.07%

No % (n) 47.07% 26.72% 21.87% 1.49%

Gender Male Female

1.35% 1.70%

50.27% 46.68%

1.27% 1.36%

49.93% 47.44%

1.22% 1.62%

49.67% 47.49%

Risk category Average VWR score Low risk (VWR < 5) Moderate risk (VWR 5–14) High risk (VWR > 14)

2.451056 (2.21754–2.684573) 72.82% (70.33244–75.17936) 25.61% (23.38549–27.96648) 1.57% (1.28385–1.91273)

2.920441 2.637482–3.2034) 67.87% (64.84481–70.75088) 29.73% (27.11027–32.48943) 2.40% (1.92534–2.99065)

3.075733 (2.808–3.343777) 66.22% (63.59228–68.7461) 31.11% (28.88152–33.42253) 2.68% (2.12573–3.36406) (continued on next page)

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Table 4 (continued) Calendar year

2008

2009

2010

POS % (n) Average age Perioperative stroke < 65 65–74 75–84 > 85

3.49 (218) 62.96298 (62.18658–63.73938) Yes % (n) 1.49% 0.98% 0.98% 0.03%

No % (n) 47.03% 26.94% 21.19% 1.35%

3.73 (256) 63.21361 (62.31094–64.11629) Yes % (n) 1.61% 1.08% 0.95% 0.09%

No % (n) 46.69% 27.01% 20.97% 1.59%

4 (223) 62.27541 (61.2296–63.32122) Yes % (n) 2.06% 0.94% 0.90% 0.06%

No % (n) 47.44% 26.12% 21.41% 1.08%

Gender Male Female

1.54% 1.95%

51.10% 45.41%

1.69% 2.04%

50.23% 46.04%

1.92% 2.08%

47.97% 48.02%

Risk category Average VWR score Low risk (VWR < 5) Moderate risk (VWR 5–14) High risk (VWR > 14)

3.11346 (2.856672–3.370248) 64.25% (61.61216–66.80263) 33.37% (31.12973–35.69555) 2.38% (1.90185–2.96764)

3.563868 (3.20926–3.918476) 61.18% (55.80407–66.29496) 35.06% (29.95562–40.53031) 3.76% (3.25373–4.34452)

3.422495 (3.069951–3.775039) 63.35% (60.16797–66.41097) 32.62% (30.05993–35.2853) 4.04% (3.2111–5.06146)

Calendar year

2011

Total

POS % (n) Average age

3.39 (2699)

Perioperative stroke < 65 65–74 75–84 > 85

3.37 (216) 63.28232 (62.5234–64.04124) Yes % (n) 1.62% 0.93% 0.80% 0.03%

No % (n) 46.55% 27.16% 21.00% 1.91%

Gender Male Female

1.68% 1.69%

49.84% 46.79%

Risk category Average VWR score

4.422664 (4.115971–4.729358) 54.74% (51.83648–57.61406) 39.09% (36.52206–41.72556) 6.17% (5.27354–7.19791)

Low risk (VWR < 5) Moderate risk (VWR 5–14) High risk (VWR > 14)

POS-perioperative stroke; CI- confidence interval; VWR-von walraven.

Table 5 Trend analysis over the years 1999–2011 for patients undergoing isolated mitral valve replacement. Calendar year

1999

2000

2001

POS % (n) Average age Perioperative stroke < 65 65–74 75–84 > 85

4.70 (181) 64.25583 No C.I. Yes % (n) 1.33% 1.77% 1.47% 0.05%

No % (n) 41.02% 30.33% 23.14% 0.88%

3.93 (165) 63.97377 No C.I. Yes % (n) 1.34% 1.38% 1.21% 0.03%

No % (n) 42.63% 31.11% 21.21% 1.09%

3.51 (146) 64.0739 (63.08866–65.05915) Yes % (n) 0.98% 1.37% 1.06% 0.08%

No % (n) 42.01% 30.12% 22.84% 1.54%

Gender Male Female

1.71% 2.99%

41.91% 53.39%

1.45% 2.48%

40.80% 55.27%

1.36% 2.15%

44.63% 51.85%

Risk category Average VWR score Low risk (VWR < 5) Moderate risk (VWR 5–14) High risk (VWR > 14)

2.046718 No C.I. 77.70% No C.I. 21.46% No C.I. 0.84% No C.I.

1.900639 No C.I. 79.77% No C.I. 19.64% No C.I. 0.59% No C.I.

179

2.090131 (1.882774–2.297489) 76.55% (74.23394–78.716) 22.57% (20.56049–24.71988) 0.88% (0.62366–1.23606) (continued on next page)

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Table 5 (continued) Calendar year

2002

2003

2004

POS % (n) Average age Perioperative stroke < 65 65–74 75–84 > 85

3.60 (143) 64.41429 (63.64161–65.18696) Yes % (n) 1.36% 1.13% 1.04% 0.02%

No % (n) 42.20% 28.04% 24.90% 1.31%

3.85 (164) 63.75943 No C.I. Yes % (n) 1.71% 1.05% 1.02% 0.02%

No % (n) 44.18% 27.64% 23.29% 1.09%

3.51 (129) 64.20736 (63.44591–64.96881) Yes % (n) 1.46% 1.15% 0.84% 0.03%

No % (n) 43.41% 26.16% 25.41% 1.55%

Gender Male Female

1.50% 2.10%

42.09% 54.31%

1.68% 2.17%

42.01% 54.14%

1.46% 2.05%

44.60% 51.89%

Risk category Average VWR score Low risk (VWR < 5) Moderate risk (VWR 5–14) High risk (VWR > 14)

2.231799 (2.081533–2.382064) 76.00% (74.12605–77.77007) 22.94% (21.18556–24.78607) 1.07% (0.80254–1.42118)

2.357547 No C.I. 74.35% No C.I. 24.60% No C.I. 1.05% No C.I.

2.573915 (2.371793–2.776037) 71.37% (69.45271–73.20489) 27.19% (25.428–29.0366) 1.44% (1.06959–1.9351)

Calendar year

2005

2006

2007

POS % (n) Average age Perioperative stroke < 65 65–74 75–84 > 85

3.57 (126) 63.74582 (62.73219–64.75944) Yes % (n) 1.64% 1.01% 0.86% 0.06%

No % (n) 42.26% 28.50% 24.30% 1.37%

3.16 (120) 63.33423 (62.46015–64.20832) Yes % (n) 1.37% 0.87% 0.91% 0.00%

No % (n) 46.40% 26.68% 22.24% 1.53%

3.69 (108) 64.41015 (63.52158–65.29873) Yes % (n) 1.40% 1.14% 1.10% 0.07%

No % (n) 43.17% 27.42% 24.00% 1.69%

Gender Male Female

1.57% 2.00%

44.14% 52.29%

1.44% 1.71%

42.21% 54.63%

1.54% 2.15%

41.13% 55.17%

Risk category Average VWR score

2.861752 (2.562694–3.160811) 68.97% (66.03855–71.74971) 28.97% (26.42729–31.65485) 2.06% (1.59753–2.65875)

3.322021 (3.029019–3.615022) 64.88% (61.98014–67.6785) 31.75% (29.22688–34.38844) 3.37% (2.6742–4.22918)

3.611386 (3.3318–3.890973) 61.26% (58.73541–63.73411) 35.13% (33.00607–37.3075) 3.61% (2.8388–4.57831)

Calendar year

2008

2009

2010

POS % (n) Average age Perioperative stroke < 65 65–74 75–84 > 85

4.33 (4.33) 63.38185 (62.53844–64.22527) Yes % (n) 1.98% 1.15% 1.23% 0.00%

No % (n) 45.24% 26.58% 22.37% 1.46%

4.85 (175) 64.38464 (63.58789–65.18138) Yes % (n) 2.20% 1.32% 1.29% 0.11%

No % (n) 42.75% 27.07% 23.41% 1.86%

5.17 (151) 63.81902 (63.01471–64.62332) Yes % (n) 3.01% 1.04% 0.95% 0.10%

No % (n) 43.21% 26.80% 23.80% 1.10%

Gender Male Female

1.85% 2.47%

42.90% 52.77%

2.04% 2.81%

42.00% 53.14%

2.39% 2.78%

39.62% 55.21%

Low risk (VWR < 5) Moderate risk (VWR 5–14) High risk (VWR > 14)

Risk category Average VWR score Low risk (VWR < 5) Moderate risk (VWR 5–14) High risk (VWR > 14)

3.544711 (3.274781–3.814641) 60.29% (57.80225–62.71972) 36.55% (34.43158–38.71795) 3.16% (2.46132–4.06127)

4.085018 (3.768723–4.401313) 57.33% (54.0766–60.52054) 37.76% (34.76541–40.85478) 4.91% (4.14571–5.80312)

4.014403 (3.626714–4.402092) 59.01% (56.07947–61.87941) 35.45% (33.1757–37.79693) 5.54% (4.43573–6.89158)

(continued on next page)

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Table 5 (continued) Calendar year

2011

Total

POS % (n) Average age

3.98 (1886)

Perioperative stroke < 65 65–74 75–84 > 85

4.21 (142) 64.38292 (63.63697–65.12888) Yes % (n) 2.15% 0.98% 1.02% 0.06%

No % (n) 42.99% 27.91% 22.99% 1.90%

Gender Male Female

2.03% 2.18%

42.31% 53.47%

Risk category Average VWR score

5.052175 (4.707478–5.396873) 49.69% (46.94554–52.44375) 42.22% (39.84012–44.63285) 8.09% (6.85823–9.51602)

Low risk (VWR < 5) Moderate risk (VWR 5–14) High risk (VWR > 14)

POS-perioperative stroke; CI- confidence interval; VWR-von walraven.

Table 6 Trend analysis over the years 1999–2011 for patients undergoing isolated mitral valve repair. Calendar year

1999

2000

2001

POS % (n) Average age Perioperative stroke < 65 65–74 75–84 > 85

2.86 (41) 57.56632 No C.I. Yes % (n) 0.98% 0.71% 1.20% 0.00%

No % (n) 50.90% 27.14% 18.42% 0.65%

2.72 (40) 59.89421 No C.I. Yes % (n) 0.82% 0.95% 0.89% 0.07%

No % (n) 50.74% 26.88% 19.05% 0.61%

3.22 (59) 59.8196 (57.81028–61.82892) Yes % (n) 1.00% 1.32% 0.80% 0.05%

No % (n) 50.44% 26.41% 19.31% 0.67%

Gender Male Female

1.54% 1.32%

54.51% 42.63%

1.31% 1.41%

57.54% 39.75%

1.70% 1.53%

55.63% 41.15%

Risk category Average VWR score Low risk (VWR < 5) Moderate risk (VWR 5–14) High risk (VWR > 14)

1.636272 No C.I. 81.41% No C.I. 18.30% No C.I. 0.28% No C.I.

1.510236 No C.I. 82.95% No C.I. 16.72% No C.I. 0.34% No C.I.

1.728009 (1.543025–1.912994) 80.48% (78.10275–82.65704) 18.75% (16.68101–21.01244) 0.77% (0.40982–1.43838)

Calendar year

2002

2003

2004

POS % (n) Average age Perioperative stroke < 65 65–74 75–84 > 85

3.36 (71) 60.15451 (58.18981–62.11922) Yes % (n) 1.24% 0.84% 1.18% 0.06%

No % (n) 49.84% 26.60% 19.31% 0.92%

2.80 (70) 61.64093 No C.I. Yes % (n) 0.89% 0.69% 1.14% 0.04%

No % (n) 49.39% 26.10% 21.01% 0.72%

2.18 (49) 61.14605 (59.89078–62.40133) Yes % (n) 0.97% 0.72% 0.50% 0.00%

No % (n) 50.42% 25.62% 20.80% 0.97%

Gender Male Female

1.57% 1.79%

54.08% 42.56%

1.37% 1.43%

57.09% 40.11%

0.78% 1.41%

57.36% 40.46%

Risk category Average VWR score Low risk (VWR < 5) Moderate risk (VWR 5–14)

1.887063 (1.683704–2.090423) 78.86% (76.48857–81.05367) 20.52% (18.36867–22.84587)

1.785089 No C.I. 78.99% No C.I. 20.34% No C.I.

181

1.840773 (1.624663–2.056884) 79.33% (76.83364–81.62433) 19.62% (17.42018–22.01994) (continued on next page)

Journal of the Neurological Sciences 382 (2017) 170–184

R. Udesh et al.

Table 6 (continued) Calendar year

2002

2003

2004

High risk (VWR > 14)

0.62% (0.36848–1.04812)

0.67% No C.I.

1.05% (0.68755–1.60108)

Calendar year

2005

2006

2007

POS % (n) Average age Perioperative stroke < 65 65–74 75–84 > 85

2.44 (75) 58.85882 (56.58869–61.12895) Yes % (n) 0.96% 0.91% 0.49% 0.10%

No % (n) 52.23% 24.94% 19.52% 0.84%

1.97 (63) 61.52192 (59.40318–63.64066) Yes % (n) 0.66% 0.55% 0.71% 0.03%

No % (n) 50.02% 27.17% 19.88% 0.98%

1.98 (54) 61.87974 (60.75331–63.00618) Yes % (n) 0.59% 0.81% 0.53% 0.07%

No % (n) 51.20% 25.90% 19.60% 1.29%

Gender Male Female

57.35% 1.37%

1.09% 40.19%

1.06% 0.92%

59.27% 38.75%

0.90% 1.08%

58.60% 39.42%

Risk category Average VWR score

1.987402 (1.743987–2.230817) 77.07% (74.20756–79.69417) 21.96% (19.35195–24.81959) 0.97% (0.67636–1.39029)

2.454919 (2.134512–2.775326) 71.35% (67.57327–74.85179) 27.31% (24.02283–30.87436) 1.33% (0.96743–1.83864)

2.520687 (2.182795–2.858578) 71.41% (67.83512–74.73357) 26.89% (23.79776–30.22474) 1.70% (1.18255–2.44121)

Calendar year

2008

2009

2010

POS % (n) Average age Perioperative stroke < 65 65–74 75–84 > 85

2.60 (82) 62.41285 (61.4391–63.38659) Yes % (n) 0.97% 0.80% 0.72% 0.07%

No % (n) 49.11% 27.18% 19.93% 1.23%

2.54 (84) 61.84858 (60.65483–63.04233) Yes % (n) 1.04% 0.82% 0.58% 0.06%

No % (n) 51.09% 26.91% 18.23% 1.27%

2.79 (75) 60.46026 (58.72145–62.19907) Yes % (n) 1.08% 0.85% 0.84% 0.00%

No % (n) 52.18% 25.41% 18.61% 1.04%

Gender Male Female

1.21% 1.40%

59.31% 38.09%

1.32% 1.23%

59.40% 38.05%

1.41% 1.37%

57.09% 40.13%

Low risk (VWR < 5) Moderate risk (VWR 5–14) High risk (VWR > 14)

Risk category Average VWR score Low risk (VWR < 5) Moderate risk (VWR 5–14) High risk (VWR > 14)

2.683783 (2.378149–2.989418) 68.07% (64.41485–71.52356) 30.37% (27.0804–33.86757) 1.56% (1.14385–2.12066)

3.013402 (2.483048–3.543757) 65.27% (56.10848–73.42291) 32.19% (24.02428–41.61372) 2.54% (2.03387–3.16803)

2.783397 (2.392265–3.174528) 67.98% (63.67949–71.98955) 29.61% (25.96829–33.52587) 2.42% (1.71231–3.39755)

Calendar year

2011

Total

POS % (n) Average age

2.56 (840)

Perioperative stroke < 65 65–74 75–84 > 85

2.49 (77) 62.08763 (60.91919–63.25607) Yes % (n) 1.00% 0.88% 0.62% 0.00%

No % (n) 50.50% 26.31% 18.76% 1.92%

Gender Male Female

1.34% 1.14%

58.18% 39.34%

Risk category Average VWR score Low risk (VWR < 5) Moderate risk (VWR 5–14) High risk (VWR > 14)

3.769283 (3.391915–4.146652) 60.01% (55.78828–64.09332) 35.79% (31.8923–39.88308) 4.20% (3.33279–5.27618)

POS-perioperative stroke; CI- confidence interval; VWR-von walraven.

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1.08–1.73, p = 0.008). Left ventricular dysfunction and CHF have been shown to increase the stroke risk due to associated coronary hemodynamic abnormalities [37].Pharmacologic treatment to improve preoperative cardiac function appears to be decisive in decreasing the risk of complications after surgery. 4.1. Study limitations This study was conducted using the National Inpatient Sample, a database that allows for analysis of large number of patients treated in the general hospital setting. This database therefore depends on proper and correct coding of diagnosis and procedures and is limited with respect to the data available for analysis. The diagnoses associated with different ICD-9 codes can overlap with one another, leading to potential inconsistency of coding. This could potentially affect the analysis by giving us false numbers. Any data on strokes, which occurred after discharge but within the 30-day post-operative mark, is unavailable. We were unable to analyze the role of subclinical silent cerebral infarcts detected by post-operative MRI post-surgery. Our study conclusions are pertaining to clinically evident strokes following mitral valve repair or replacement. There could be considerable variability in the pre-operative and post-operative care of patients among the different institutions and this may have affected the outcome rates as well. Supplementary data to this article can be found online at https:// doi.org/10.1016/j.jns.2017.10.004. 5. Conclusion Carotid disease is a significant risk factor for perioperative strokes following mitral valve surgery. Pre-operative screening with carotid Doppler to identify high-risk patients appears to be warranted. Further prospective clinical studies are needed to look into risk stratification of patients for better patient selection and the question of whether carotid revascularization procedures before or after mitral valve surgery will be beneficial in reducing stroke rates. Sources of funding None. Conflicts of interest None. Acknowledgements None. References [1] J. Bucerius, J.F. Gummert, M.A. Borger, T. Walther, N. Doll, J.F. Onnasch, S. Metz, V. Falk, F.W. Mohr, Stroke after cardiac surgery: a risk factor analysis of 16,184 consecutive adult patients, Ann. Thorac. Surg. 75 (2) (2003) 472–478. [2] A. Russo, F. Grigioni, J.F. Avierinos, W.K. Freeman, R. Suri, H. Michelena, R. Brown, T.M. Sundt, M. Enriquez-Sarano, Thromboembolic complications after surgical correction of mitral regurgitation incidence, predictors, and clinical implications, J. Am. Coll. Cardiol. 51 (12) (2008) 1203–1211. [3] M. Heras, J.H. Chesebro, V. Fuster, W.J. Penny, D.E. Grill, K.R. Bailey, G.K. Danielson, T.A. Orszulak, J.R. Pluth, F.J. Puga, et al., High risk of thromboemboli early after bioprosthetic cardiac valve replacement, J. Am. Coll. Cardiol. 25 (5) (1995) 1111–1119. [4] C.W. Hogue Jr., S.F. Murphy, K.B. Schechtman, V.G. Davila-Roman, Risk factors for early or delayed stroke after cardiac surgery, Circulation 100 (6) (1999) 642–647. [5] Harvest 1 - executive summary, Adult Cardiac Surg. Database 2016 (2016). [6] R.H. Mehta, K.A. Eagle, L.P. Coombs, E.D. Peterson, F.H. Edwards, F.D. Pagani, G.M. Deeb, S.F. Bolling, R.L. Prager, R. Society of thoracic surgeons national cardiac, influence of age on outcomes in patients undergoing mitral valve replacement, Ann. Thorac. Surg. 74 (5) (2002) 1459–1467. [7] A.M. Gillinov, D.M. Cosgrove, Mitral valve repair, Oper. Tech. Thorac. Cardiovasc. Surg. 3 (2) (1998) 95–108.

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