
==== Front
J Cardiothorac Surg
J Cardiothorac Surg
Journal of Cardiothoracic Surgery
1749-8090
BioMed Central London

3009
10.1186/s13019-024-03009-x
Research
Stroke after heart valve surgery: a single center institution report
Alwaqfi Nizar nralwaqfi@just.edu.jo

AlBarakat Majd M.
Qariouti Hala
Ibrahim Khalid
alzoubi Nabil
grid.37553.37 0000 0001 0097 5797 Faculty of Medicine, Faculty of medicine, Jordan University of Science and Technology, Irbid, Jordan
9 9 2024
9 9 2024
2024
19 5181 1 2024
13 8 2024
© The Author(s) 2024
2024
https://creativecommons.org/licenses/by-nc-nd/4.0/ Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
Introduction

Stroke is a potentially debilitating complication of heart valve replacement surgery, with rates ranging from 1 to 10%. Despite advancements in surgical techniques, the incidence of postoperative stroke remains a significant concern, impacting patient outcomes and healthcare resources. This study aims to investigate the incidence, risk factors, and outcomes of in-hospital adverse neurologic events, particularly stroke, following valve replacement. The analysis focuses on identifying patient characteristics and procedural factors associated with increased stroke risk.

Methods

This retrospective study involves a review of 417 consecutive patients who underwent SVR between January 2004 and December 2022. The study cohort was extracted from a prospectively recorded cardiac intensive care unit database. Preoperative and perioperative data were collected, and subjects with specific exclusion criteria were omitted from the analysis. The analysis includes demographic information, preoperative risk factors, and perioperative variables.

Results

The study identified a 4.3% incidence of postoperative stroke among SVR patients. Risk factors associated with increased stroke susceptibility included prolonged cardiopulmonary bypass time, aortic cross-clamp duration exceeding 90 min, prior stroke history, diabetes mellitus, and mitral valve annulus calcification. Patients undergoing combined procedures, such as aortic valve replacement with mitral valve replacement or coronary artery bypass grafting with AVR and MVR, (OR = 10.74, CI:2.65–43.44, p-value = < 0.001) and (OR = 11.66, CI:1.02–132.70, p-value = 0.048) respectively, exhibited elevated risks. Internal carotid artery stenosis (< 75%) and requiring prolonged inotropic support were also associated with increased stroke risk(OR = 3.04, CI:1.13–8.12, P-value = 0.026). The occurrence of stroke correlated with extended intensive care unit stay (OR = 1.12, CI: 1.04–1.20, P-value = 0.002) and heightened in-hospital mortality.

Conclusion

In conclusion, our study identifies key risk factors and underscores the importance of proactive measures to reduce postoperative stroke incidence in surgical valve replacement patients.

Keywords

Stroke
Heart valve surgery
Valve surgery complications
issue-copyright-statement© BioMed Central Ltd., part of Springer Nature 2024
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pmcIntroduction

Stroke is a rare but still a potentially crippling complication of heart valve replacement surgery with risk dependent on patient characteristics and concomitant procedures. Stroke rates after surgical valve replacement (SVR) have ranged widely from 1 to 10% [1–10].

Studies of clinical stroke-complicating cardiac surgeries have reported increased duration and cost of hospitalization, dramatically elevated in-hospital mortality, and a high rate of severe disability in survivors [4, 8, 9].

Several studies have evaluated risk factors and postoperative neurologic complications after heart valve surgery, though the results are conflicting or incomplete mainly due to a low number of interventions or a low number of variables. Also, the low incidence of this postoperative key event limits the power of most published papers. Some studies have reported the association between prolonged cardiopulmonary bypass (CPB) and the development of postoperative stroke, while others have questioned its significance [11–14]. Other reported risk factors include age, concomitant atrial fibrillation (AF), history of cerebrovascular (CV) disease, concomitant carotid artery (CA) stenosis and aortic atherosclerosis, preoperative left ventricular (LV) dysfunction, concomitant procedures and lack of postoperative anticoagulation. [10, 15–22] Recently, there is evidence that the rate of neurologic complications after SVR has been increasing, likely because of the willingness of surgeons to operate on older and higher-risk patients. [1, 16] As such the current literature provides heterogeneous rates of adverse in-hospital neurologic complications after SVR. This heterogeneity, especially from the clinical trials, has raised the issue of whether the real-life stroke rate after heart valve surgery is different from that in the trial setting.

To address this issue and to the best of our knowledge, in our institution, stroke incidence, risk factors, and outcomes were not reported. We aimed to assess the incidence of in-hospital adverse neurologic events after SVR (with or without coronary artery bypass grafting [CABG]) and to identify patient and disease factors associated with stroke. In addition, the impact of postoperative stroke on length of hospital stay (LOS) and in-hospital mortality was evaluated.

Materials and methods

This study is a retrospective review of the clinical, operative, and outcome data that is part of the prospectively recorded cardiac intensive care unit (CICU) database. The present analysis includes all replacement valve surgeries performed between January 2004 and December 2022. Preoperative and perioperative data were retrospectively collected. After isolation of data, subjects were excluded if they had undergone CA stenting or endarterectomy within the previous 6 weeks; had any significant neurological disease, defined as the incidence of stroke or transient ischemic attack (TIA) within the preceding 6 months; had symptomatic or asymptomatic severe occlusive CA disease requiring concomitant endarterectomy/stenting. Also, patients who underwent valve repair, additional procedures on the aorta, and redo valve surgery were excluded from the study. Additionally, patients were excluded if an additional surgical procedure on the ascending aorta was performed.

The studied population consisted of 417 consecutive patients. Two groups were identified; Group 1 consisted of 18 patients who had a postoperative stroke, and group 2 consisted of the remaining patients (399) in the cohort. This work was approved by the ethical committee in the institution and the patient`s signature was waived.

Preoperative data

Patient’s medical records were reviewed for prior stroke; results of brain computerized tomography (CT) scan or magnetic resonance imaging (MRI), when available, or presence of unresolved neurological deficit, body mass index (BMI), New York Heart Association (NYHA) classification; symptomatic patients or on anti-failure treatment, diabetes mellitus (DM); with the majority being type 2 diabetes managed with oral hypoglycemic agents, hypertension; previously diagnosed and on anti-hypertensive treatment, chronic renal impairment (CRI); creatinine ≥ 1.5 mg/dl or on chronic dialysis, peripheral vascular disease (PVD); positive history of intermittent claudication or a documented clinical evidence of peripheral ischemia, left ventricular ejection fraction (LVEF); by either angiography or echocardiography, number of diseased coronary arteries; based on coronary angiogram and operative reports.

CA duplex scanning or CT scan angiography was performed routinely for most of the patients (80% of the studied cohort); almost 8% had severe CA stenosis (luminal narrowing ≥ 75%) and 24.5% had moderate disease. Patients with severe CA stenosis were sent for surgical or percutaneous intervention before valve surgery.

Perioperative antithrombotic treatment

Patients who were taking aspirin (100 mg) continued this medication without interruption preoperatively. Heparin (3.0 mg/kg) was administered intravenously before cardiopulmonary bypass (CPB) to maintain an activated clotting time (ACT) greater than 400 s. At the end of the procedure, heparin was neutralized with protamine sulfate (3.0 mg/kg). Additional protamine was administered if ACT remained above 140 s before chest closure. Neither aprotinin nor tranexamic acid was used in any patient. Transfusion of packed red blood cells, fresh frozen plasma, and platelets was determined based on bleeding volume, International Normalized Ratio (INR) levels, and platelet counts.

Postoperatively, patients received warfarin with bridging using unfractionated heparin or enoxaparin until the INR reached therapeutic levels. The target INR was 2.5 to 3 times normal for patients with St. Jude, Carbomedics, or Medtronic Hall aortic valves, and 3 to 3.5 times normal for patients with St. Jude, Carbomedics, or Medtronic Hall mitral valves. Patients with more than one prosthetic valve were maintained at a target INR of 3.5 to 4 times normal. The addition of daily aspirin (100 mg) was at the discretion of the treating physician.

Patients with bioprosthetic valves received warfarin for 1 to 3 months postoperatively, followed by lifelong aspirin therapy. In patients with bioprosthetic valves and atrial fibrillation, warfarin was continued as clinically indicated.

Intraoperative data

Assessment of the ascending aorta was performed using digital palpation. It is noted that none of the stroke patients included in this study had documented atherosclerotic disease of the ascending aorta; therefore, this variable was not specifically assessed.

Standard techniques were employed for cardiopulmonary bypass (CPB), ensuring perfusion was maintained at 2.0 to 2.4 L/min/m². Systemic perfusion pressure was carefully regulated within the range of 60 to 80 mmHg throughout the procedure. Myocardial viability was preserved through the use of cold antegrade potassium cardioplegia and topical hypothermia techniques. Furthermore, body temperature was meticulously controlled and maintained between 28 °C and 32 °C to optimize surgical conditions and patient outcomes.

Neurological complications

Stroke was defined as any new focal neurological dysfunction of presumed vascular origin lasting more than 24 h. A neurological assessment is routinely done by the surgical team if patients are extubated within 24 h. Patients with positive neurological examination, suspected neurological deficit, and/or prolonged time on ventilator are usually assessed by the neurologists. Stroke diagnosis was based on clinical findings and brain imaging by CT scan or MRI.

Statistical analysis

Continuous variables are presented as either mean ± standard deviation or median [interquartile range], depending on the distribution normality. Categorical variables are displayed as counts (percentages). Odds ratios (OR) and 95% confidence intervals (CI) were calculated for categorical data comparisons. A p-value of less than 0.05 was deemed statistically significant. All statistical analyses were conducted using R software (version 3.4.0, R Foundation, Vienna, Austria).

Results

Table 1 displays the demographics and univariate analyses of patient characteristics in groups 1 (stroke) and 2 (no stroke). There were 17 (4.3%) patients in group 1 and 399 patients in group 2. The average age for group 1 was 59.5 (± 9.44) years, whereas for group 2 it was 51.6 (± 15.3) years, yielding a statistically significant difference (p = 0.003). The mean BMI for group 1 was 28.8 (± 4.36), while for group 2 it was 22.0 (± 5.1%).

Table 1 Univariate analysis of clinical characteristics of patients in groups 1 and 2

	Stroke	No stroke	p-value	
Age		59.5(9.44)*	51.6 (15.3)*	0.003	
BMI		28.8 (4.36)*	26.4(5.24)*	0.037	
Gender	Male	7(38.9%)	220 (55.1%)	0.176	
Smoking		3(16.7%)	129(32.3%)	0.162	
COPD		1(5.6%)	21(5.3%)	0.957	
Hypertension		11(61.1%)	177 (44.5%)	0.165	
Hyperlipidemia		5(27.8%)	75(18.8%)	0.344	
Diabtes Mellitus		9(50.0%)	81(20.3%)	0.003	
History of stroke		4 (22.2%)	24(6.0%)	0.007	
NYHA 3–4 (pre-operative)		4(22.2%)	73(18.3%)	0.675	
Peripheral vascular disease		1(5.6%)	24(6.0%)	0.934	
Atrial fibrillation (preoperative)		6(33.3%)	79(19.8%)	0.163	
Renal Impairment (preoperative)		2(11.1%)	27(6.8%)	0.478	
Type of operation	AVR	3 (16.7%)	175 (43.9%)		
	MVR	2 (11.1%)	124 (31.1%)		
	AVR + MVR	7 (38.9%)	38 (9.5%)		
	AVR + CABG	2 (11.1%	24 (6.0%)		
	MVR + CABG	3 (16.7%)	33 (8.3%)		
	AVR + MVR + CABG	1 (5.6%)	5 (1.3%)	< 0.001	
Aortic valve calcification		7(38.9%)	99(24.8%)	0.180	
Mitral valve annulus calcification		8(44.4%)	71(17.8%)	0.005	
Type of valve used (Aortic)	Biological	5 (5.4%)	88 (94.6%)		
	Mechanical	7 (4.7%)	142 (95.3%)	0.813	
Type of valve used (Mitral)	Biological	5 (10%)	45 (90%)		
	Mechanical	8 (5%)	151 (95%)	0.205	
*Mean and standard deviation AVR: aortic valve replacement MVR: mitral valve replacement BMI: body mass index COPD: chronic obstructive pulmonary disease NYHA: New York Heart Association CABG: coronary artery bypass grafting AVR: aortic valve replacement MVR: mitral valve replacement

Approximately 44.4% of patients in the postoperative stroke group exhibited mitral valve annulus calcification (MVAC), whereas this figure was only 17% in the other group. Additionally, 50% of the patients with stroke had DM, in contrast to only 20% in the other group. The most prevalent type of operation in the stroke group was AVR combined with MVR, whereas in the other group, AVR alone was the predominant procedure.

Table 2. presents the Crude Odds Ratios (OR) and their corresponding 95% Confidence Intervals (CI) for factors associated with postoperative Stroke. Patients undergoing procedures such as AVR with MVR, MVR with CABG, and AVR with MVR and CABG exhibited elevated risks of postoperative stroke, with odds ratios of 10, 5, and 11 respectively.

Table 2 Crude odds ratio (OR) and their 95% confidence intervals (CI) for the factors Associated with Stroke

		OR crude	CI (95%)	P- Value	
Gender	Male	0.5178	0.1967–1.363	0.183	
Smoking		0.4186	0.1191–1.4716	0.175	
COPD		1.0588	0.1344–8.3416	0.957	
Hypertension		1.9621	0.7453–5.1656	0.172	
Hyperlipidemia		1.6615	0.5748–4.8032	0.349	
Diabetes mellitus		3.9259	1.5098–10.2082	0.005	
History of stroke		4.4643	1.3645–14.6064	0.013	
NYHA 3–4 (pre-operative)		1.2759	0.4081–3.9888	0.675	
Peripheral vascular disease		0.9167	0.117–7.1819	0.934	
Atrial Fibrillation (pre-operative)		2.02	0.3763–7.8822	0.484	
Serum creatinine (Pre-operative)		0.99	0.9908–1.009	0.988	
Hematocrit (peri-operative)		1.14	1.03–1.259	0.013	
Ejection fraction% (Pre-operative)		1.02	1.0012–1.0437	0.038	
Internal carotid artery stenosis

50-<75%

		4.12	1.3887–12.2761	0.011	
Left atrium diameter (cm)		1.41	0.94323–2.1102	0.094	
Operation type	AVR	1			
	MVR	0.94	0.15498–5.7117	0.947	
	AVR + MVR	10.74	2.65761–43.4481	< 0.001	
	AVR + CABG	4.86	0.77263–30.5843	0.092	
	MVR + CABG	5.30	1.02579–27.415	0.047	
	AVR + MVR + CABG	11.66	1.02566–132.7054	0.048	
Aortic valve calcification		1.92	0.7277–5.1098	0.187	
Mitral valve Annulus Calcification		3.69	1.4088–9.6952	0.008	
Pump Time (> 120 min)		6.31	2.30729–17.2703	< 0.001	
Aorta clamp time (> 90 min)		6.26	2.3546–16.6754	< 0.001	
Re-exploration for bleeding		2.14	0.4631–9.9076	0.33	
Temporary pacing (post-operative)		1.73	0.6681–4.497	0.258	
Prolonged inotropes support		3.04	1.1394–8.1296	0.026	
Serum creatinine level (post-operative)		1.00	0.9958–1.0062	0.719	
Renal impairment (Post-operative)		2.35	0.8085–6.8637	0.116	
Dialysis (post-operative)		2.01	0.2467–16.4662	0.513	
Atrial fibrillation (post-operative)		1.73	0.056–3.3052	0.417	
Pneumonia/Sepsis (post-operative)		2.50	0.5357–11.6672	0.244	
ICU stay (days)		1.12	1.0443–1.2036	0.002	
Length of hospital stay (days)		1.03	0.9889–1.0854	0.136	
Mortality (peri-operative)		7.05	1.7804–27.9528	0.005	
* COPD: Chronic Obstructive Pulmonary Disease, NYHA: New York Heart Association, Cm: Centimeter, AVR: Aortic Valve Replacement, MVR: Mitral Valve Replacement, CABG: Coronary Artery Bypass Grafting, ICU: Intensive Care Unit

Patients with internal CA stenosis ranging from 50% to less than 75% demonstrated a substantially increased susceptibility to stroke, with an odds ratio of 4.129 (CI: 1.3887–12.2761) and a p-value of 0.011. Similarly, individuals with DM were associated with a heightened risk, displaying an odds ratio of 3.9259 (CI: 1.5098–10.2082) and a p-value of 0.005.

Patients with a prior history of stroke exhibited a higher risk with an odds ratio of 4.4643 and a CI of (1.3645–14.6064), with a p-value of 0.013. Furthermore, CPB exceeding 120 min demonstrated a significantly elevated risk in comparison to durations less than 120 min, with an odds ratio of 6.312 and a CI of 0.4631–9.9076 (p < 0.001). Additionally, aortic cross-clamping for more than 90 min demonstrated a heightened risk with an odds ratio of 6.2661 and a CI of 2.3546–16.6754, with a p-value less than 0.001.

Patients requiring prolonged inotropic support for more than 48 h demonstrated a significantly increased risk, with an odds ratio of 3.04 (95% CI: 1.14–8.13) and a p-value of 0.026. Furthermore, the occurrence of stroke was associated with an extended stay in the CICU, indicated by an odds ratio of 1.12 (95% CI: 1.04–1.20) and a p-value of 0.002.

The stroke group exhibited a significantly elevated postoperative mortality risk, with an OR of 7.05 (95% confidence interval [CI]: 1.78–27.95), indicating a substantial increase in risk. The corresponding p-value was 0.005.

Discussion

In our study, we assessed the occurrence of postoperative stroke in 417 consecutive SVR patients which included different valve replacement and combined surgeries. We found that 4.3% of patients experienced postoperative stroke, matching what was reported by Raffa et al. [23] with a sample size of 2121 patients. This drastic complication was significantly associated with prolonged CICU stay and increased operative mortality, this association was clearly established in our analysis, underscoring the importance of identifying potential risk factors to mitigate postoperative neurological complications. The exact reason for this high mortality associated with stroke remains unclear. We think most of stroke patients are elderly with multiple comorbidities, spend long time in CICU on ventilator, which make them prone for major complications, particularly respiratory failure and sepsis. [10, 18]

The etiology of postoperative stroke after cardiac surgery is multifactorial, with embolism being the predominant cause, while intraoperative hypotension and hemorrhage are less common. [24] Most of our patients had a stroke, however, we couldn’t identify embolization or perioperative hypotension as the possible cause. Also, nothing was mentioned in most of the operative notes about the status of the ascending aorta; this may be related to the observed negligible incidence of atherosclerotic changes of the ascending aorta in our patients, which is the major source of emboli to the brain.

In our study having a unilateral ICA stenosis (< 75%) was significantly associated with an increased risk of stroke, which may be necisating further preoperative assessment of the extracardiac arterial system.

Our analysis indicated that a history of prior stroke was a robust preoperative predictor of stroke, with an OR of approximately 4.5. A history of stroke may indicate underlying pathological conditions within the cerebrovascular arteries. Bucerius et al. [10] conducted a similar study involving 16,184 patients and reported a stroke incidence of 16.8% in patients with cerebrovascular disease undergoing similar surgeries. In our study, the incidence was even higher, with our analysis revealing that 22.2% (4 out of 18) of patients who experienced postoperative stroke had a history of previous strokes. These findings underscore the necessity for more thorough preoperative screening.

In our study, DM was significantly associated with postoperative stroke, a relationship that has also been reported by several investigators. This further emphasizes the significance of this association that places patients at increased risk of embolization from atherosclerotic lesions as well as impaired auto-regulation of cerebral blood flow. [10, 17–19]

In our sample, it was observed that over half of the stroke patients had a history of hypertension. This observation raises the possibility of an association between hypertension and stroke, consistent with the findings of some previous reports. [10] However, our analysis did not yield a statistically significant result, which may be attributed to the limited sample size.

Severe perioperative hemodilutional anemia may be a critical factor in the pathogenesis of postoperative ischemia and stroke. In our study, perioperative anemia was a risk factor of postoperative stroke. This was reported by Kulier et al. [26]. However, different other studies didn’t confirm this finding [27, 28].

In our study, we revealed that patients with MVAC were at 3.6 times greater risk compared to those without. Several studies have highlighted that MVAC introduces considerable technical complexity to procedures involving the mitral valve, increased risk of embolization, and potentially leads to increased risks not only in operative mortality but also in perivalvular leak and atrioventricular groove disruption [20–22]. It is worth noting that Kaneko et al. [25] in their retrospective study of 197,737 unique MV procedures conducted at 1158 participating institutions, did not achieve statistically significant results in this context. This underscores the critical need for additional research in this area.

In our study, patients with CPB time longer than two hours and aortic cross-clamp longer than one and a half hours were associated with postoperative stroke. These prolonged times usually indicate operating on complicated combined procedures or due to unexpected unfavorable anatomy and intraoperative complications. This association has been reported by other investigators. [10]

Conclusion

Stroke poses a significant challenge following surgical valve replacement (SVR), affecting approximately 5% of patients. The incidence of stroke can vary based on surgical factors. From our single-center database analysis, several independent risk factors for perioperative stroke were identified. Understanding these factors is crucial for devising strategies to mitigate stroke risk through rigorous pre-, intra-, and post-operative protocols.

It is important to acknowledge the retrospective nature of this analysis, which inherently carries limitations such as potential biases in data collection. The study’s retrospective design and the relatively low number of stroke cases may limit the generalizability of our findings. Furthermore, the etiology of strokes (embolic, thrombotic, or hypoperfusive) could not be definitively determined from our data.

Limitations

Our study highlights age, atrial fibrillation (AF), prior stroke history, and double valve surgery (AVR + MVR) as significant factors associated with postoperative stroke, which are known confounders. Despite these biases, our study provides new insights into stroke risk following surgical valve replacement, emphasizing the need for targeted preventive strategies.

Additionally, the study did not systematically track patients who underwent left atrial appendage occlusion (LAAO), limiting our ability to assess its impact on stroke outcomes.

Another limitation is the low incidence of postoperative strokes, with only 18 out of 417 patients experiencing this event over 18 years. This small sample size limits the statistical power and generalizability of our findings. However, our study still offers valuable insights into the incidence and risk factors of postoperative strokes, contributing to future research and clinical practices.

Acknowledgements

None.

Author contributions

M.M.A and N.A validated the idea. H.Q collected the data. M.M.A. analyzed the data and wrote the manuscript. N.A, K.I, and N.A did the supervision and reviewing of the manuscript.

Funding

We received no funding for this study.

Data availability

No datasets were generated or analysed during the current study.

Declarations

Conflict of interest

The authors declare no conflict of interest.

Ethics approval and consent to participate

The Institutional Review Board (IRB) of Jordan University of Science and Technology approved the study with the number 519 of the year 2023. Consent forms were obtained from the patients before participation and the study followed the World Health Organization Declaration on the Ethical Principles of Helsinki for Medical Research on Humans.

Competing interests

The authors declare no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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