Author Interviews, Heart Disease, JACC, Stroke, Surgical Research / 12.08.2016
New Onset Atrial Fibrillation Strongest Predictor of Stroke After TAVR
MedicalResearch.com Interview with:
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Dr. Josep Rodés-Cabau[/caption]
Josep Rodés-Cabau, MD
Director, Catheterization and Interventional Laboratories
Quebec Heart and Lung Institute
Professor, Faculty of Medicine, Laval University
Quebec City, Quebec, Canada
MedicalResearch.com: What is the background for this study?
Response: Transcatheter aortic valve replacement (TAVR) is increasingly used in patients with severe aortic stenosis deemed at prohibitive or high surgical risk. Recently, a randomized trial demonstrated the non-inferiority of TAVR compared to surgical aortic valve replacement in intermediate risk patients for the outcome of death and disabling stroke at 2 years. Therefore, TAVR indications are likely to expand to younger and lower risk patients in the near future.
While the short-term (30-day) cerebrovascular event (CVE) rate post-TAVR has decreased over time, it remains the most dreadful complication of TAVR, and still occurs in 2% to 3% of patients. A few dedicated studies identified numerous predictors of CVE which mainly differ from one study to another. However, identifying the risk factors of CVE is of paramount relevance in clinical practice to implement preventive strategies, either instrumental (embolic protection devices) or pharmacological in high-risk patients. Thus, we performed a systematic review and meta-analysis using random-effect models to provide pooled estimates of sixteen (8 patient-related and 8 procedural-related) clinically-relevant predictors of CVE within 30 days post TAVR.
Dr. Josep Rodés-Cabau[/caption]
Josep Rodés-Cabau, MD
Director, Catheterization and Interventional Laboratories
Quebec Heart and Lung Institute
Professor, Faculty of Medicine, Laval University
Quebec City, Quebec, Canada
MedicalResearch.com: What is the background for this study?
Response: Transcatheter aortic valve replacement (TAVR) is increasingly used in patients with severe aortic stenosis deemed at prohibitive or high surgical risk. Recently, a randomized trial demonstrated the non-inferiority of TAVR compared to surgical aortic valve replacement in intermediate risk patients for the outcome of death and disabling stroke at 2 years. Therefore, TAVR indications are likely to expand to younger and lower risk patients in the near future.
While the short-term (30-day) cerebrovascular event (CVE) rate post-TAVR has decreased over time, it remains the most dreadful complication of TAVR, and still occurs in 2% to 3% of patients. A few dedicated studies identified numerous predictors of CVE which mainly differ from one study to another. However, identifying the risk factors of CVE is of paramount relevance in clinical practice to implement preventive strategies, either instrumental (embolic protection devices) or pharmacological in high-risk patients. Thus, we performed a systematic review and meta-analysis using random-effect models to provide pooled estimates of sixteen (8 patient-related and 8 procedural-related) clinically-relevant predictors of CVE within 30 days post TAVR.
Dr. Richard Leigh[/caption]
Dr. Richard Leigh MD
Neuro Vascular Brain Imaging Unit
National Institute of Neurological Disorders and Stroke
National Institutes of Health, Bethesda, MD
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Patients who suffer an ischemic stroke have limited treatment options. One of the reasons for this is that our treatments can sometimes make the stroke worse by transforming the ischemic stroke into a hemorrhagic stroke. In our study we identified a new piece of information that we can extract from the patient’s MRI scan that informs us on the risk of having a hemorrhage.
Dr. Gregoire Boulouis[/caption]
Dr. Gregoire Boulouis MD MS
Research Fellow at Massachusetts General Hospital / Harvard Med. School
Boston, Massachusetts
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Boulouis: Hemorrhagic Stroke or Intracerebral hemorrhage (ICH) still has a poor prognosis. A substantial proportion of patients will experience ongoing intracranial bleeding and their hematomas will grow in size in the first hours following presentation, a phenomenon called 'hemorrhage epxansion'. Patients with hemorrhage expansion have been shown to have significantly worse clinical outcome. If all baseline ICH characteristics (location, initial hemorrhage volume, ..) are non modifiable at the time of diagnosis, hemorrhage expansion, however, represents one of the few potential targets to improve outcome in ICH patients. An accurate selection of patients at high risk of expansion is needed to optimize patients' selection in expansion targetted trials and, eventually, to help stratifying the level of care at the acute phase.
In this study, we investigated whether the presence of non-contrast Computed Tomography hypodensities within the baseline hematoma, a very easily and reliably assessed imaging marker, was associated with more hemorrhage expansion.
A total of 1029 acute phase ICH patients were included ; approximately a third of them demonstrated CT hypodensities at baseline. In this population, CT hypodensities were independently associated with hemorrhage expansion with an odds ratio of 3.42 (95% CI 2.21-5.31) for expansion in fully adjusted multivariable model.
Dr. Alessandro Biffi[/caption]
Alessandro Biffi, MD
Behavioral Neurology and Neuropsychiatry
Departments of Neurology and Psychiatry
Massachusetts General Hospital / Harvard Medical School
MedicalResearch.com: What is the background for this study?
Dr. Biffi: Intracerebral Hemorrhage (ICH) is the most severe form of stroke. It is a form of hemorrhagic (i.e. bleeding) stroke that accounts for ~ 15% of all acute cerebrovascular conditions, affecting ~ 70,000 Americans every year. However, because of its severity it is responsible for almost half of all stroke-related disability worldwide. Survivors of ICH are at very high risk for cognitive impairment (up to and including dementia) following the acute cerebral bleeding event. However, we possess very limited understanding of the time dynamics and risk factors for post-ICH dementia. In particular, prior to our study it was unclear whether the acute cerebral injury due to ICH would be the only mechanism potentially responsible for subsequent development of dementia.
This question is motivated by prior observations suggesting that Intracerebral Hemorrhage represents the acute manifestation of cerebral small vessel disease, a progressive degenerative disorder of small caliber arteries of the central nervous system.
There exist two major subtypes of small vessel disease:
1) cerebral amyloid angiopathy, caused by the deposition of a toxic protein product, beta-amyloid, in the blood vessels (in a process similar to the formation of beta-amyloid plaques that cause Alzheimer's disease);
2) arteriolosclerosis, caused by long-standing elevated blood pressure. ICH survivors have been previously shown to harbor very severe small vessel disease, which has been linked to dementia in patients without cerebral bleeding.
Our hypothesis was that early-onset dementia (occurring in the first 6 months after ICH) is a manifestation of the acute neurological damage associated with cerebral bleeding, whereas delayed onset dementia (developing beyond 6 months from the acute ICH event) is associated with known markers of small vessel disease, including imaging findings on CT/MRI and genetic markers (such as the APOE gene).
Dr. George Howard[/caption]
George Howard, Dr.P.H.
Professor of biostatistics
Birmingham School of Public Health
University of Alabama
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Howard: What has been known for many decades is that death rates from stroke are much higher in the black than white population, particularly between the ages of 45 – 65 (or maybe even a little older). These racial differences in stroke are among the greatest disparities for any disease, clearly it is a priority to reduce this disparity.
However, there are two reasons more blacks could die from a disease:
1) more blacks get the disease, or
2) once you get the disease, it is more likely to kill blacks.
The implications of knowing which of these is the major contributor is profound. If the driving force is more blacks are having more stroke, then we need to focus out attention on activities before stroke occur. For example, prevention of the greater prevalence of hypertension and diabetes in blacks, and also reducing the differences in the control of blood pressure and glucose. However, if the driving force is a higher chance of death in blacks once stroke occur, then we need to focus on the disparities in how black stroke patients are cared for compared to white stroke patients. That is, the former requires community-based efforts, while the latter requires hospital-based efforts.
What we found was that nearly all the difference was that blacks are having more strokes ... not that they are more likely to die once stroke occurs.
Dr. David Earnest[/caption]
David Earnest, Ph.D.
Professor in the Department of Neuroscience and Experimental Therapeutics
Texas A&M Health Science Center College of Medicine
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Earnest: When body clocks are disrupted, as they are when people engage in shift work or go to bed and get up at radically different times every few days, more severe ischemic strokes can result.
MedicalResearch.com: What should readers take away from your report?
Dr. Earnest: Whenever possible, go to bed and get up at the same time each day and keep regular mealtimes. If you do need to keep an irregular schedule, it is especially important to be mindful of stroke risk and try especially hard to eliminate other risk factors, such as hypertension and obesity.
Dr. Kazem Rahimi[/caption]
Kazem Rahimi, DM, MSc
Oxford Martin School
University of Oxford
United Kingdom
MedicalResearch.com: What is the background for this study?
Dr. Rahimi: Vascular dementia is the second most common cause of dementia and is increasing in prevalence worldwide. Vascular dementia often occurs after stroke and can cause apathy, depression, and a decline in cognitive function, and can eventually result in death. High blood pressure (BP) has been identified as a potential risk factor for the development of vascular dementia. However, previous studies, which have been small in size, have reported conflicting results on the relationship between blood pressure and vascular dementia.
Prof. Craig Anderson[/caption]
Professor Craig Anderson
Professor of Stroke Medicine and Clinical Neuroscience
Sydney Medical School at the University of Sydney
Institute of Neurosciences of Royal Prince Alfred Hospital
MedicalResearch.com: What is the background for this study?
Prof. Anderson: Intravenous use of the clot-busting drug, alteplase (or rtPA), at a dose of 0.9 mg/kg body weight is the only proven medical treatment of acute ischemic stroke. However, a major drawback to the treatment is an increased risk of major bleeding in the brain, or intracerebral hemorrhage (ICH), that occurs in about 5% of cases, and can be fatal. This balance of effectiveness (recovery from disability) and risks (ICH, and bleeding elsewhere and uncommon drug allergic reactions) has led to much of the controversy over the net benefit of the drug. The optimal dose of the drug has never been established, but the Japanese drug safety regulatory authority, has approved a lower dose (0.6mg/kg) on the basis of a small, non-randomized, open study which showed comparable outcomes and lower risk of ICH than historical controls. This ‘east-west’ divide over the approved dose of alteplase has led to much variation in the dose of alteplase used in clinical practice in Asia – according to a doctor’s perceived risk of ICH in individual patients and the affordability of this relatively expensive treatment in low resource settings. Data from the Get-with-the Guidelines Quality Registry in the United States suggests Asian patients are at higher risk of ICH after standard-dose alteplase than non-Asians.
Our research aimed to resolve this uncertainty over the optimal dose of alteplase, as an international, active-comparator, open-label, blinded outcome assessed, clinical trial of low-dose (0.6 mg/kg) versus standard-dose (0.9mg/kg) in 3310 patients recruited from over 100 hospitals in 13 countries between 2012 and 2015.
Dr. Ben Freedman[/caption]
Dr. Ben Freedman OAM
Deputy Director Research Strategy, Heart Research Institute/Charles Perkins Centre
Professor of Cardiology, Sydney Medical School
Head Vascular Biology Anzac Research Institute
Honorary VMO, Concord Repatriation General Hospital
University of Sydney
MedicalResearch.com: What is the background for this study?
Dr. Freedman: Guidelines recommend that patients with atrial fibrillation (AF) at high enough risk for stroke should be treated with anticoagulant. Anticoagulant drugs are remarkably effective in reducing stroke risk by about two thirds, and death by between a quarter and a third. Unfortunately, strokes can still occur when patients are prescribed anticoagulant for Atrial Fibrillation, and it is often presumed this residual risk of stroke represents treatment failure, though there are few data about this important issue.
MedicalResearch.com: What are the main findings?
Dr. Freedman: We were able to compare the risk of stroke in a cohort of patients with AF commenced on anticoagulant, with a very large closely-matched cohort seen in general practice at the same time but without AF. This is a unique comparison. We found that the residual risk of stroke in such anticoagulant-treated patients was virtually identical to that in the matched control cohort. The implication is that the residual risk of stroke may not be treatment failure, but the risk of non-cardioembolic stroke in people of a similar age and stroke risk profile but without Atrial Fibrillation. The residual risk of death in those on anticoagulant was higher than the matched controls, and intermediate between the control rate and the mortality rate for untreated AF.
