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Journal of the American Heart... Apr 2022Background A relevant proportion of patients with suspected coronary artery disease undergo invasive coronary angiography showing normal or nonobstructive coronary... (Meta-Analysis)
Meta-Analysis Review
Background A relevant proportion of patients with suspected coronary artery disease undergo invasive coronary angiography showing normal or nonobstructive coronary arteries. However, the prevalence of coronary microvascular disease (CMD) and coronary spasm in patients with nonobstructive coronary artery disease remains to be determined. The objective of this study was to determine the prevalence of coronary CMD and coronary vasospastic angina in patients with no obstructive coronary artery disease. Methods and Results A systematic review and meta-analysis of studies assessing the prevalence of CMD and vasospastic angina in patients with no obstructive coronary artery disease was performed. Random-effects models were used to determine the prevalence of these 2 disease entities. Fifty-six studies comprising 14 427 patients were included. The pooled prevalence of CMD was 0.41 (95% CI, 0.36-0.47), epicardial vasospasm 0.40 (95% CI, 0.34-0.46) and microvascular spasm 24% (95% CI, 0.21-0.28). The prevalence of combined CMD and vasospastic angina was 0.23 (95% CI, 0.17-0.31). Female patients had a higher risk of presenting with CMD compared with male patients (risk ratio, 1.45 [95% CI, 1.11-1.90]). CMD prevalence was similar when assessed using noninvasive or invasive diagnostic methods. Conclusions In patients with no obstructive coronary artery disease, approximately half of the cases were reported to have CMD and/or coronary spasm. CMD was more prevalent among female patients. Greater awareness among physicians of ischemia with no obstructive coronary arteries is urgently needed for accurate diagnosis and patient-tailored management.
Topics: Coronary Angiography; Coronary Artery Disease; Coronary Vasospasm; Coronary Vessels; Female; Humans; Male; Microcirculation; Microvascular Angina; Prevalence
PubMed: 35301851
DOI: 10.1161/JAHA.121.023207 -
Neurocritical Care Jun 2022Our objective was to compare the effectiveness of intravenous and enteral nimodipine in preventing poor outcome from delayed cerebral ischemia in patients with... (Meta-Analysis)
Meta-Analysis Review
Our objective was to compare the effectiveness of intravenous and enteral nimodipine in preventing poor outcome from delayed cerebral ischemia in patients with subarachnoid hemorrhage. We performed a systematic search and a network meta-analysis using the following databases: PubMed, Scopus, the Cochrane Central Register of Controlled Trials, and Google Scholar. Risk of Bias 2 tool was used to assess risk of bias of included studies. A ranking among methods was performed on the basis of the frequentist analog of the surface under the cumulative ranking curve. Published studies that met the following population, intervention, comparison, outcomes and study (PICOS) criteria were included: patients with subarachnoid hemorrhage aged 15 years or older (P); nimodipine, intravenous and oral formulation (I); placebo or no intervention (C); poor outcome measured at 3 months (defined as death, vegetative state, or severe disability), case fatality at 3 months, delayed cerebral ischemia, delayed ischaemic neurologic deficit, and vasospasm measured with transcranial Doppler or digital subtraction angiography (O); and randomized controlled trials (S). No language or publication date restrictions were applied. Ten studies were finally included, with a total of 1527 randomly assigned patients. Oral and intravenous nimodipine were both effective in preventing poor outcome, delayed cerebral ischemia, and delayed ischaemic neurological deficit. Neither treatment was effective in improving case fatality. Evolving clinical protocols over a 30-year period and the risk of bias of the included studies may limit the strength of our results. Enteral and intravenous nimodipine may have a similar effectiveness in terms of preventing poor outcome, delayed cerebral ischemia, and delayed ischaemic neurological deficit. More research may be needed to fully establish the role of intravenous nimodipine in current clinical practice.
Topics: Brain Ischemia; Cerebral Infarction; Humans; Network Meta-Analysis; Nimodipine; Randomized Controlled Trials as Topic; Subarachnoid Hemorrhage; Treatment Outcome; Vasospasm, Intracranial
PubMed: 35419702
DOI: 10.1007/s12028-022-01493-4 -
Neurocritical Care Oct 2019Intrathecal nicardipine has been shown to have some efficacy for the treatment of symptomatic cerebral vasospasm in aneurysmal subarachnoid hemorrhage (aSAH). We...
Intrathecal nicardipine has been shown to have some efficacy for the treatment of symptomatic cerebral vasospasm in aneurysmal subarachnoid hemorrhage (aSAH). We performed a PRISMA-based systematic review of intrathecal nicardipine for the treatment of cerebral vasospasm in aneurysmal subarachnoid hemorrhage. A total of 825 articles were reviewed. After duplicates were removed and the search criteria was applied, 9 articles remained that were eligible for inclusion and analysis. 377 patients received a total of 6,596 injections of intrathecal nicardipine for aSAH-related cerebral vasospasm. The cumulative ventriculostomy-associated infection risk was 6%. Intrathecal nicardipine injections for aSAH-related cerebral vasospasm appears efficacious and safe. Administration of 4 mg of nicardipine every 12 hours was the most commonly reported dosing regimen. Intrathecal nicardipine decreases mean flow velocities on transcranial Doppler and reduces angiographic and clinical vasospasm. The infection risk appears to be in-line with studies in which rates of EVD-related infections have been reported.
Topics: Blood Flow Velocity; Cerebrovascular Circulation; Humans; Injections, Intraventricular; Injections, Spinal; Nicardipine; Subarachnoid Hemorrhage; Treatment Outcome; Ultrasonography, Doppler, Transcranial; Vasodilator Agents; Vasospasm, Intracranial; Ventriculostomy
PubMed: 30607826
DOI: 10.1007/s12028-018-0659-9 -
Circulation Mar 2015Myocardial infarction with nonobstructive coronary arteries (MINOCA) is a puzzling clinical entity with no previous evaluation of the literature. This systematic review... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Myocardial infarction with nonobstructive coronary arteries (MINOCA) is a puzzling clinical entity with no previous evaluation of the literature. This systematic review aims to (1) quantify the prevalence, risk factors, and 12-month prognosis in patients with MINOCA, and (2) evaluate potential pathophysiological mechanisms underlying this disorder.
METHODS AND RESULTS
Quantitative assessment of 28 publications using a meta-analytic approach evaluated the prevalence, clinical features, and prognosis of MINOCA. The prevalence of MINOCA was 6% [95% confidence interval, 5%-7%] with a median patient age of 55 years (95% confidence interval, 51-59 years) and 40% women. However, in comparison with those with myocardial infarction associated with obstructive coronary artery disease, the patients with MINOCA were more likely to be younger and female but less likely to have hyperlipidemia, although other cardiovascular risk factors were similar. All-cause mortality at 12 months was lower in MINOCA (4.7%; 95% confidence interval, 2.6%-6.9%) compared with myocardial infarction associated with obstructive coronary artery disease (6.7%, 95% confidence interval, 4.3%-9.0%). Qualitative assessment of 46 publications evaluating the underlying pathophysiology responsible for MINOCA revealed the presence of a typical myocardial infarct on cardiac magnetic resonance imaging in only 24% of patients, with myocarditis occurring in 33% and no significant abnormality in 26%. Coronary artery spasm was inducible in 27% of MINOCA patients, and thrombophilia disorders were detected in 14%.
CONCLUSIONS
MINOCA should be considered as a working diagnosis with multiple potential causes that require evaluation so that directed therapies may improve its guarded prognosis.
Topics: Coronary Vessels; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Myocardial Infarction; Prevalence; Prognosis; Risk Factors; Survival Rate
PubMed: 25587100
DOI: 10.1161/CIRCULATIONAHA.114.011201 -
The Laryngoscope Apr 2019Nimodipine is a calcium channel blocker that has been used to treat hypertension and vasospasm. Emerging evidence in the literature suggests that it is neuroprotective... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Nimodipine is a calcium channel blocker that has been used to treat hypertension and vasospasm. Emerging evidence in the literature suggests that it is neuroprotective by reducing cellular apoptosis after neuronal injury and promoting axonal sprouting at the nodes of Ranvier.
OBJECTIVES
To conduct a systematic review of the usage of nimodipine in cranial nerve injury and to perform a meta-analysis to estimate the efficacy of nimodipine on functional recovery of the injured cranial nerves.
METHODS
Literature search was performed in eight databases using preferred reporting items for systematic reviews and meta analyses (PRISMA) guidelines. Human studies that used nimodipine as a monotherapy for treating cranial nerve injury were included for review. Cranial nerve function recovery was the primary outcome measure.
RESULTS
672 records were screened and 58 full texts in English were assessed. Nine studies were included in the final review. 5 of these, including 110 participants who received nimodipine for either recurrent laryngeal nerve or facial nerve injury and 556 controls, were used for meta-analysis. Nimodipine significantly increased the odds of vocal fold motion recovery (odds ratio [OR] 13.73, 95% confidence interval [CI] 6.21, 30.38, P < .01), and the odds of facial motion recovery (OR 2.78, 95% CI 1.20, 6.44, P = .02). Overall, nimodipine-treated patients had significantly higher odds of recovering vocal fold or facial motion compared with controls (OR 6.09, 95% CI 3.41, 10.87, P < .01).
CONCLUSION
Existing evidence supports the positive effect of nimodipine on vocal fold and facial motion recovery after injury. Future research should focus on randomized clinical trials comparing recovery rates between nimodipine- and placebo-treated groups. Laryngoscope, 129:943-951, 2019.
Topics: Calcium Channel Blockers; Cranial Nerve Injuries; Face; Humans; Nimodipine; Recovery of Function; Treatment Outcome; Vocal Cords
PubMed: 30450691
DOI: 10.1002/lary.27530 -
Stroke Jun 2022Aneurysmal subarachnoid hemorrhage (aSAH) is associated with high mortality and morbidity. We aimed to determine the relative benefits of pharmacological prophylactic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Aneurysmal subarachnoid hemorrhage (aSAH) is associated with high mortality and morbidity. We aimed to determine the relative benefits of pharmacological prophylactic treatments in patients with aneurysmal subarachnoid hemorrhage by performing a network meta-analysis of randomized trials.
METHODS
We searched Medline, Web of Science, Embase, Scopus, ProQuest, and Cochrane Central to February 2020. Pairs of reviewers independently identified eligible trials, extracted data, and assessed the risk of bias. Eligible trials compared the prophylactic effects of any oral or intravenous medications or intracranial drug-eluting implants to one another or placebo or standard of care in adult hospitalized patients with confirmed aneurysmal subarachnoid hemorrhage. We used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to assess the certainty of the evidence.
RESULTS
We included 53 trials enrolling 10 415 patients. Nimodipine likely reduces all-cause mortality compared to placebo (odds ratio [OR],0.73 [95% CI, 0.53-1.00]; moderate certainty; absolute risk reduction (ARR), -3.35%). Nimodipine (OR, 1.46 [95% CI, 1.07-1.99]; high certainty; absolute risk increase, 8.25%) and cilostazol (OR, 3.73 [95% CI, 1.14-12.18]; moderate certainty; absolute risk increase, 23.15%) were the most effective treatments in improving disability at the longest follow-up. Compared to placebo, clazosentan (10 mg/kg; OR, 0.39 [95% CI, 0.22-0.68]; high certainty; ARR, -16.65%), nicardipine (OR, 0.48 [95% CI, 0.24-0.94]; moderate certainty; ARR, -13.70%), fasudil (OR, 0.55 [95% CI, 0.31-0.98]; moderate certainty; ARR, -11.54%), and magnesium (OR, 0.66 [95% CI, 0.46-0.94]; high certainty; ARR, -8.37%) proved most effective in reducing the likelihood of delayed cerebral ischemia.
CONCLUSIONS
Nimodipine and cilostazol are likely the most effective treatments in preventing morbidity and mortality in patients with aneurysmal subarachnoid hemorrhage. Clazosentan, nicardipine, fasudil, and magnesium showed beneficial effects on delayed cerebral ischemia and vasospasm but they were not found to reduce mortality or disability. Future trials are warranted to elaborately investigate the prophylactic effects of medications that may improve mortality and long-term functional outcomes, such as cilostazol and clazosentan.
REGISTRATION
URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42019122183.
Topics: Adult; Brain Ischemia; Cilostazol; Humans; Magnesium; Morbidity; Network Meta-Analysis; Nicardipine; Nimodipine; Randomized Controlled Trials as Topic; Subarachnoid Hemorrhage; Vasospasm, Intracranial
PubMed: 35354302
DOI: 10.1161/STROKEAHA.121.035699 -
Neurosurgical Focus Nov 2017OBJECTIVE Little is known regarding the natural history of posttraumatic vasospasm. The authors review the pathophysiology of posttraumatic vasospasm (PTV), its... (Review)
Review
OBJECTIVE Little is known regarding the natural history of posttraumatic vasospasm. The authors review the pathophysiology of posttraumatic vasospasm (PTV), its associated risk factors, the efficacy of the technologies used to detect PTV, and the management/treatment options available today. METHODS The authors performed a systematic review in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines using the following databases: PubMed, Google Scholar, and CENTRAL (the Cochrane Central Register of Controlled Trials). Outcome variables extracted from each study included epidemiology, pathophysiology, time course, predictors of PTV and delayed cerebral ischemia (DCI), optimal means of surveillance and evaluation of PTV, application of multimodality monitoring, modern management and treatment options, and patient outcomes after PTV. Study types were limited to retrospective chart reviews, database reviews, and prospective studies. RESULTS A total of 40 articles were included in the systematic review. In many cases of mild or moderate traumatic brain injury (TBI), imaging or ultrasonographic studies are not performed. The lack of widespread assessment makes finding the true overall incidence of PTV a difficult endeavor. The clinical consequences of PTV are important, given the morbidity that can result from it. DCI manifests as new-onset neurological deterioration that occurs beyond the timeframe of initial brain injury. While there are many techniques that attempt to diagnose cerebral vasospasm, digital subtraction angiography is the gold standard. Some predictors of PTV include SAH, intraventricular hemorrhage, low admission Glasgow Coma Scale (GCS) score (< 9), and young age (< 30 years). CONCLUSIONS Given these results, clinicians should suspect PTV in young patients presenting with intracranial hemorrhage (ICH), especially SAH and/or intraventricular hemorrhage, who present with a GCS score less than 9. Monitoring and regulation of CNS metabolism following TBI/ICH-induced vasospasm may play an important adjunct role to the primary prevention of vasospasm.
Topics: Brain Injuries, Traumatic; Brain Ischemia; Cerebral Hemorrhage; Humans; Intracranial Hemorrhages; Subarachnoid Hemorrhage; Vasospasm, Intracranial
PubMed: 29088959
DOI: 10.3171/2017.8.FOCUS17431 -
Neurosurgical Focus Mar 2022Aneurysmal subarachnoid hemorrhage (aSAH) accounts for a relatively small portion of strokes but has the potential to cause permanent neurological deficits. Vasospasm... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Aneurysmal subarachnoid hemorrhage (aSAH) accounts for a relatively small portion of strokes but has the potential to cause permanent neurological deficits. Vasospasm with delayed ischemic neurological deficit is thought to be responsible for much of the morbidity associated with aSAH. This has illuminated some treatment options that have the potential to target specific components of the vasospasm cascade. Intrathecal management via lumbar drain (LD) or external ventricular drain (EVD) offers unique advantages in this patient population. The aim of this review was to provide an update on intrathecal vasospasm treatments, emphasizing the need for larger-scale trials and updated protocols using data-driven evidence.
METHODS
A search of PubMed, Ovid MEDLINE, and Cochrane databases included the search terms (subarachnoid hemorrhage) AND (vasospasm OR delayed cerebral ischemia) AND (intrathecal OR intraventricular OR lumbar drain OR lumbar catheter) for 2010 to the present. Next, a meta-analysis was performed of select therapeutic regimens. The primary endpoints of analysis were vasospasm, delayed cerebral ischemia (DCI), cerebral infarction, and functional outcome.
RESULTS
Twenty-nine studies were included in the analysis. There were 10 studies in which CSF drainage was the primary experimental group. Calcium channel antagonists were the focus of 7 studies. Fibrinolytics and other vasodilators were each examined in 6 studies. The meta-analysis included studies examining CSF drainage via LD (n = 4), tissue plasminogen activator in addition to EVD (n = 3), intraventricular nimodipine (n = 2), and cisternal magnesium (n = 2). Results showed that intraventricular nimodipine decreased vasospasm (OR 0.59, 95% CI 0.37-0.94; p = 0.03). Therapies that significantly reduced DCI were CSF drainage via LD (OR 0.47, 95% CI 0.25-0.88; p = 0.02) and cisternal magnesium (OR 0.27, 95% CI 0.07-1.02; p = 0.05). CSF drainage via LD was also found to significantly reduce the incidence of cerebral infarction (OR 0.35, 95% 0.24-0.51; p < 0.001). Lastly, functional outcome was significantly better in patients who received CSF drainage via LD (OR 2.42, 95% CI 1.39-4.21; p = 0.002).
CONCLUSIONS
The authors' results showed that intrathecal therapy is a safe and feasible option following aSAH. It has been shown to attenuate cerebral vasospasm, reduce the incidence of DCI, and improve clinical outcome. The authors support the use of intrathecal management in the prevention and rescue management of cerebral vasospasm. More randomized controlled trials are warranted to determine the best combination of pharmaceutical agents and administration route in order to formulate a standardized treatment approach.
Topics: Brain Ischemia; Drainage; Humans; Subarachnoid Hemorrhage; Tissue Plasminogen Activator; Vasospasm, Intracranial
PubMed: 35231885
DOI: 10.3171/2021.12.FOCUS21629 -
Journal of Neurosurgery. Pediatrics Sep 2023Delayed cerebral ischemia (DCI) associated with vasospasm is well described in the setting of aneurysmal subarachnoid hemorrhage (SAH). In addition, DCI is very...
OBJECTIVE
Delayed cerebral ischemia (DCI) associated with vasospasm is well described in the setting of aneurysmal subarachnoid hemorrhage (SAH). In addition, DCI is very infrequently encountered in patients who have undergone resection of a brain tumor with unclear pathophysiology. The occurrence of DCI in the pediatric population is exceedingly rare, and outcomes in this population have, to the authors' knowledge, never been systematically reviewed. Therefore, the authors present what is to their knowledge the largest series of pediatric patients with this complication and systematically reviewed the literature for individual participant data.
METHODS
The authors conducted a retrospective review of 172 sellar and suprasellar tumors in pediatric patients who underwent surgery at the Montreal Children's Hospital between 1999 and 2017 to identify cases of vasospasm occurring after tumor resection. Descriptive statistics, including patient characteristics, intraoperative and postoperative findings, and outcome status, were collected. A systematic review was also conducted using three databases (PubMed, Web of Science, Embase) to identify reported cases available in the literature of vasospasm after tumor resection in children and collect individual participant data on these patients for further analysis.
RESULTS
Six patients treated at Montreal Children's Hospital were identified, with an average age of 9.5 years (range 6-15 years). The prevalence of vasospasm after tumor resection was 3.5% (6/172). Vasospasm in all 6 patients occurred after craniotomy was performed to treat a suprasellar tumor. The average interval from surgery to symptoms was 3.25 days (range 12 hours-10 days). The most common tumor etiology was craniopharyngioma, seen in 4 cases. Extensive tumor encasement of blood vessels requiring significant operative manipulation was described in all 6 patients. A rapid decrease in serum sodium (exceeding 12 mEq/L/24 hrs or below 135 mEq/L) was seen in 4 patients. On final follow-up, 3 patients were left with significant disability, and all patients had persistent deficits. A systematic review of the literature revealed a total of 10 other patients whose characteristics and treatment were compared with those of the 6 patients treated at Montreal Children's Hospital.
CONCLUSIONS
Vasospasm after tumor resection in children and youth is likely a rare entity, with a prevalence of 3.5% in this case series. Suprasellar tumor location (particularly craniopharyngioma tumor etiology), significant encasement of blood vessels by the tumor, and postoperative hyponatremia may be predictive factors. Outcome is poor, with most patients having significant persistent neurological deficits.
Topics: Adolescent; Humans; Child; Craniopharyngioma; Subarachnoid Hemorrhage; Brain Ischemia; Brain Neoplasms; Craniotomy; Pituitary Neoplasms; Vasospasm, Intracranial
PubMed: 37327188
DOI: 10.3171/2023.3.PEDS22373 -
Frontiers in Neurology 2023Vasospasm and cerebral ischemia after aneurysmal subarachnoid hemorrhage are associated with mortality and poor neurological outcomes. We studied the efficacy of all...
BACKGROUND
Vasospasm and cerebral ischemia after aneurysmal subarachnoid hemorrhage are associated with mortality and poor neurological outcomes. We studied the efficacy of all available strategies targeting vasospasm and cerebral ischemia on outcomes in a network meta-analysis.
METHODS
We searched EMBASE and MEDLINE databases from 1 January 1990 and 28 November 2021 according to PRISMA guidelines. Randomized controlled trials and longitudinal studies were included. All curative or preventive strategies targeting vasospasm and/or cerebral ischemia were eligible. A network meta-analysis was performed to compare all interventions with one another in a primary (randomized controlled trials only) and a secondary analysis (both trials and longitudinal studies). Mortality by 3 months was the primary outcome. Secondary outcomes were vasospasm, neurological outcome by 3 months, and dichotomized as "good" or "poor" recovery according to each study definition.
RESULTS
A total of 2,382 studies were screened which resulted in the selection of 192 clinical trials (92 (47.9%) and 100 cohorts (52.1%) and the inclusion of 41,299 patients. In randomized controlled studies, no strategy decreased mortality by 3 months. Statins (0.79 [0.62-1]), tirilazad (0.82 [0.69-0.97]), CSF drainage (0.47 [0.29-0.77]), and clazosentan (0.51 [0.36-0.71]) significantly decreased the incidence of vasospasm. Cilostazol was the only treatment associated with improved neurological outcomes by 3 months in the primary (OR 1.16, 95% CI [1.05-1.28]) and secondary analyses (OR 2.97, 95% CI [1.39-6.32]).
DISCUSSION
In the modern era of subarachnoid hemorrhage, all strategies targeting vasospasm failed to decrease mortality. Cilostazol should be confirmed as a treatment to improve neurological outcomes. The link between vasospasm and neurological outcome appears questionable.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=116073, identifier: PROSPERO CRD42018116073.
PubMed: 37662039
DOI: 10.3389/fneur.2023.1217719