Archive for Março, 2014

Um grupo de pesquisadores holandeses avaliaram os pacientes com HSA por ruptura de aneurisma cerebral, especificamente os indivíduos que tinham dois ou mais familiares de primeiro grau com este diagnóstico. O follow-up do estudo de coorte foi de 10 anos consecutivos (2003 a 2013). Os métodos de screening usados foram angioressonância ou angiotomografia (exames não invasivos). Os resultados do estudo foram publicados recentemente online ASAP pela Lancet Neurology.


Os fatores de risco mais relevantes encontrados na população com exames positivos no primeiro screening foram tabagismo (OR 2,7; 95% CI 1,2-5,9), história de aneurisma prévio (OR 3,9, CI 1,2-12,7) e história familiar de aneurisma cerebral (3,5, 1,6-8,1).

A frequência de diagnóstico de aneurismas cerebrais foi de 11% no primeiro screening (n=458, 95% CI 9-14), de 8% (CI 5-12) no segundo screening (n=261), 5% (CI 2-11) no terceiro screening (n=128) e novamente 5% (CI 1-14) no quarto screening (n=63).

História de aneurisma cerebral prévio foi o único fator de risco com significância estatística para o achado de aneurisma cerebral no screening de seguimento (HR 4·5, CI 1·1—18·7). Em jovens < 30 anos que foram investigados (n=129), aneurismas foram identificados em 5% (95% CI 2-10).

Os autores concluem o seguinte: Em indivíduos com história familiar de aneurisma cerebral, o follow-up prolongado (maior de 10 anos) é justificado, mesmo quando dois exames iniciais são normais.


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Borderline-high blood pressure, known as prehypertension, was associated with an increased risk for stroke in a new meta-analysis that included more than 700,000 participants.

Although the increased risk was largely driven by high-range prehypertension, the risk was also increased in people with low-range prehypertension.

The study, published online in Neurology on March 12, was conducted by a Chinese group. The authors conclude that: “In this study, we had sufficient power to demonstrate that the risk of stroke is increased even in individuals with relatively mild BP elevations. Our findings reaffirm the importance of the definition of ‘prehypertension’ rather than being ‘normal’ for individuals with BP of 120–139/80–89 mm Hg.”

Senior author, Dingli Xu, MD, Southern Medical University in Guangzhou, China, said the findings had important clinical and public health implications. “Considering the high proportion of the population who have higher than normal blood pressure (30-50% of the population), successful treatment of this condition could prevent many strokes and make a major difference in public health,” he stated.

“Important” Study

Commenting for Medscape Medical News, Ralph L. Sacco, MD, University of Miami Miller School of Medicine, Florida, said, “This is an important study that adds to the accumulating evidence that borderline elevated blood pressure levels, also called prehypertension, significantly increases the risk of stroke.”

He stated: “This meta-analysis provides further evidence to physicians and patients that we need to take blood pressure seriously even at borderline levels. The first step is lifestyle modification with increasing physical activity, losing weight and eating healthy including reducing salt consumption. If these do not work or are unsuccessful, then medications may be warranted, particularly among those with elevated risk of stroke such as family history, diabetes, or other vascular conditions.”

Dr. Sacco noted that the study is timely because there has been some controversy regarding the recently released JNC8 recommendations that loosened the level of blood pressure defined as abnormal for those older than age 60 years and moved the level to a systolic pressure of 150 mm Hg.

“But in this study the effects of borderline elevations of blood pressure were significantly increased for those under 55 as much as those over 55,” Dr. Sacco pointed out. He added that the American Heart Association has defined ideal blood pressure as 120/80 mm Hg, and the study also confirms this as the optimal level.

In the Neurology paper, the authors explain that previous studies on the risk for stroke with prehypertension have shown mixed results. Therefore, a comprehensive meta-analysis of prospective cohort studies that examined the association between prehypertension and stroke, as well as the heterogeneity of risk within this category, may help to clarify this issue.




Côté R et al. Neurology 2014 Feb 4.

Long-term aspirin plus clopidogrel wasn’t better than aspirin alone.

In the previously published SPS3 trial, 3000 patients who experienced lacunar strokes during the previous 6 months were randomized to receive aspirin alone or aspirin plus clopidogrel. During several years of follow-up, dual antiplatelet therapy did not prevent recurrent stroke and increased risk for major hemorrhage and death (NEJM JW Neurol Aug 29 2012). Now, in a post hoc analysis from this study, researchers present data on the 838 patients who already had been taking prophylactic aspirin at the time of the lacunar stroke that qualified them for the trial.

Outcomes in this subgroup mirrored those of the larger study. During mean follow-up of 3.5 years, the annual stroke rate was 3% in both the aspirin monotherapy and dual antiplatelet therapy treatment groups. However, annual mortality was higher with dual therapy than with aspirin alone (2.9% vs. 1.4%; P=0.004), and gastrointestinal bleeding was more common with dual therapy.


In this analysis, aspirin plus clopidogrel was not more effective than aspirin alone for preventing subsequent strokes in patients with previous lacunar strokes that occurred during aspirin therapy. Note that SPS3 patients were randomized an average of 2.5 months after their index lacunar strokes. In contrast, in the recently published CHANCE trial (NEJM JW Neurol Jun 26 2013), short-term dual therapy was more effective than aspirin alone in patients with transient ischemic attack or minor stroke who were randomized within 24 hours; in that study, no distinction was made between lacunar strokes and other stroke subtypes.

Wang Y et al. N Engl J Med 2013 Jun 26.

Results of a study in China suggest that it might. 

To compare the effects of aspirin plus clopidogrel with aspirin alone in minor stroke or transient ischemic attack (TIA), more than 100 centers in China recruited a total of 5170 patients with a diagnosis of “high-risk” TIA or minor stroke within 24 hours of symptom onset. High-risk TIA was defined as a score of ≥4 on the ABCD2 scale, which is based on age, blood pressure, and other clinical variables. Minor stroke was defined as a score of ≤3 on the NIH Stroke Scale score.

All patients received aspirin (75–300 mg) on day 1 and 75 mg of aspirin through day 21. Those randomized to dual antiplatelet therapy received 300 mg of clopidogrel on day 1 and 75 mg on days 2 through 90, with aspirin placebo on days 22 through 90. Those randomized to aspirin alone continued on 75 mg of aspirin daily though day 90, with clopidogrel placebo on days 1 through 90.

During the 90-day follow-up period, there was a significant, 32% relative reduction in the rate of stroke with dual antiplatelet therapy (11.7% with aspirin alone, 8.2% with the combination; hazard ratio, 0.68) and a significant reduction in the combination of fatal or disabling stroke (HR, 0.75). Major extracranial or intracranial hemorrhages did not differ (0.3% in both groups).


Some treatments initially used for cardiac disease (e.g., thrombolysis and statins) have percolated into the prevention and treatment of stroke. Other treatments commonly used for cardiac disease, such as intravenous heparin, have not been proven useful for stroke.

What about dual antiplatelet therapy, which is effective for acute coronary syndromes? This study showed an impressive 32% relative and 3.5% absolute reduction in the rate of stroke with dual antiplatelet therapy. Asian populations differ from others with respect to the pathophysiology of stroke, such as greater frequency of intracranial stenosis. A North American study with a similar design is in progress (the POINT trial). If the second study confirms the benefits of dual antiplatelet therapy, another “cardiac” treatment could soon be applied to patients with cerebrovascular disease.


Transcranial Doppler (TCD) saline studies were better than transesophageal echocardiography (TEE) at identifying patent foramen ovale (PFO), even large PFOs, in patients with cryptogenic stroke, a new study shows, and may allow risk stratification that could guide decisions on whether or not to consider PFO closure.

“What we found is that transcranial Doppler saline studies are better both for diagnosing, because it’s more sensitive, but also for risk stratifying,” senior author J. David Spence, MD, director of the Stroke Prevention and Atherosclerosis Research Centre, Robarts Research Institute at the University of Western Ontario, London, Canada, concluded.

TEE is still required for defining other cardiac causes of stroke, such as left atrial appendage thrombus or valve problems, he added, “so these techniques are complementary.”

The results were presented here at the American Stroke Association International Stroke Conference (ISC) 2014.

Paradoxical Embolism

“Paradoxical embolism is something that cardiologists tend not to believe in and neurologists know happens,” Dr. Spence explained during a press conference here. Clots associated with deep venous thrombosis pass through a PFO and are thought to cause stroke in about 4.5% to 5% of patients.

Unfortunately, 25% of the population has a PFO, which means PFO is an innocent bystander in about 80% of stroke patients. Even among patients with cryptogenic stroke, about half of these PFOs are incidental, he said. The question of whether to close the PFO to prevent paradoxical embolism has proved difficult to answer. To date, randomized trials, including CLOSURE-I, RESPECT, and PC Trial, were all negative.

Meta-analysis of all the randomized trials to date has not shown a benefit of PFO closure. “And I think that’s probably because of this issue of statistical power,” Dr. Spence said. “If half the patients don’t have the problem you’re treating, it’s very hard to show benefit.”

The procedure is also not without risk; complications include atrial fibrillation, embolization of the device causing aortic valve or femoral artery occlusion, or thrombus on the device, some cases of which have been fatal.

“So we need to identify among patients with PFO which are the ones that are more likely to have a stroke, and therefore more likely to respond to treatment” with PFO closure, he said.

In 2008, an article was published outlining several factors associated with cryptogenic strokes that should raise the index of suspicion for paradoxical embolism, Dr. Spence noted. Factors include a young patient without another established cause of the stroke, dyspnea or tachycardia at onset, loud P2 or pulmonic regurge, history of long car or airplane trips or sitting at a computer, previous deep venous thrombosis, varicose veins or pulmonary embolism, Valsalva maneuver, sleep apnea, or waking with a stroke.

Small early studies suggested features that might flag PFOs that might be considered high risk for events, including a larger shunt, presence of septal mobility, or atrial septal aneurysm, he noted, but in larger studies, septal mobility or aneurysm did not predict events.

TCD is already used in clinical practice for a number of purposes, including to identify stenosis of intracranial vessels, to detect vasospasm in the setting of subarachnoid hemorrhage, and for embolus detection for risk stratification of patients with asymptomatic carotid stenosis.

In the current study, Dr. Spence and colleagues compared TCD saline studies (TCDSS) with TEE in identifying PFO in a series of 340 patients with cryptogenic stroke who were referred to the Urgent TIA Clinic at their institution after they were suspected of having a paradoxical embolism.

All patients had confirmed right-to-left shunts on TCDSS, and 280 patients also had TEE available. “It turned out that transesophageal echo, which has been regarded as the gold standard, missed 15% of the (right-to-left shunts), and even more surprising is it missed quite big shunts,” Dr. Spence noted.

TCD shunt grades are measured using the Spencer scale, ranging from grade 0, in which no microemboli indicative of a right-to-left shunt are detected, to grade V, in which 300 or more microemboli are detected during a TCDSS. The visual and audio output after injection of the bubbles is “not subtle, they’re definite,” he noted.

Of the 15.4% of right-to-left shunts missed by TEE, 25% were high-grade shunts, “and they were the shunts that we showed were associated with prediction of risk,” Dr. Spence said. “So patients with a shunt grade greater than 3 were significantly more likely to have a stroke or TIA during the follow up of almost 4 years than ones who had smaller shunts ( = .008).”

Survival free of stroke or TIA was not predicted by the presence of a shunt on TEE ( P = .8) or by the presence of mobile or aneurysmal atrial septum ( P = .38), he noted.

Opportunity for Risk Stratification?

Asked for comment on the findings, Ralph Sacco, MD, from the Miller School of Medicine at the University of Miami, in Florida, and past president of the American Heart Association, told Medscape Medical News that PFO “remains a conundrum for neurologists and cardiologists.

The study by Dr. Spence and colleagues looks, however, at diagnostic differences in the techniques used to identify PFO. “He found that transcranial Doppler was as good or even better than transesophageal echo for diagnosing a PFO in unexplained stroke patients, and those that had the bigger shunts based on the TCD grading seemed to have a greater risk of a recurrent stroke,” Dr. Sacco noted.”We know that some patients with a PFO and an unexplained stroke have a paradoxical embolism,” he said. “The problem is some unexplained strokes have a PFO, but the PFO may or may not be related to the stroke, and trying to tease apart in which patients the PFO and the stroke are related is still difficult.”

“What we still don’t know is how we reduce that risk,” he added. Randomized trials of PFO closure have not at the moment shown a significant reduction of stroke risk, but they have also been difficult to do, have taken a long time for recruitment, “and sometimes they recruit patients that may or may not have a stroke related to the PFO, and that’s sort of the problem.”

This study does imply, though, that TCD might be used to risk-stratify patients to select a group at higher risk with larger PFOs who might be randomly assigned into trials, he said.

Dr. Sacco noted that previous work by his own group in a smaller series had also suggested that TCD might be better than TEE to identify PFO in cryptogenic stroke patients. However, they had not linked TCD characteristics to outcomes, as Dr. Spence and colleagues have done in this study.

The “golden question,” he said, is what to do once a PFO is found. “If they’re a younger patient and it’s a big PFO, and it looks like there’s a clot in the leg that could have been the source, usually then I would anticoagulate. If it’s an older patient and you’re not clear, antiplatelets suffice.” Guidelines usually call first for antiplatelets and to then move on to anticoagulation if the patient fails antiplatelet therapy with another event, Dr. Sacco noted.

“The larger the PFO in a younger patient with what really looks like a paradoxical embolism, the more that I would get a cardiologist involved to consider closing it,” he said.

Dr. Spence reports no relevant financial relationships.

International Stroke Conference (ISC) 2014. Abstract LB10. Presented February 14, 2014.

Forame Oval Patente e AVC isquêmico

O que é Forame Oval? O forame oval é um pequeno orifício localizado no meio da parede de músculo que divide os dois átrios (cavidades presentes normalmente no coração) no nosso coração. Em condições normais, este orifício costuma se fechar ao nascimento ou nos primeiros meses / anos de vida. Em cerca de 25% dos adultos normais, entretanto, pode acontecer deste forame oval não fechar, deixando uma pequena comunicação entre os átrios cardíacos, e esta situação é o que se chama de Forame Oval Patente (FOP – sigla em português) .

Figura mostrando o Forame Oval Patente (patent foramen ovale - em inglês).

Forame Oval Patente e AVC. Diversos estudos com pessoas jovens (< 55 anos) que tiveram um AVC isquêmico (AVCi) sem causa determinada mostraram que nesta situação, a incidência de FOP sobe dos 25% encontrados em pessoas normais, para 40%. Algumas características do FOP, como o tamanho dda comunicação, a quantidade de shunt (desvio de sangue) existente entre os átrios e a presença ou não de um aneurisma ou membrana redundante no septo interatrial, são os principais fatores levados em consideração para estimar o risco maior ou menor de recorrência associada aos casos de AVCi indeterminado.

Tratamento. Existem três possibilidades para o tratamento de pacientes com AVCi sem causa determinada que possuem o Forame Oval Patente:

1 – Tratamento clínico, com medicamentos orais antiagregantes ou anticoagulantes, que afinam o sangue e evitam a formação de trombos, responsáveis pela ocorrência do AVCi.

2 – Tratamento cirúrgico, realizado por cirurgiões cardíacos, onde há a abertura do esterno (osso do tórax), abertura do coração e correção cirúrgica do defeito da parede / do septo interatrial.

3 – Tratamento endovascular, realizado por cardiologistas especializados em Hemodinâmica, onde o FOP é corrigido por cateterismo, com a colocação de uma prótese endovascular que fecha o foramem sem a necessidade de cirurgia aberta do coração.

Até meados de 2013, as evidências apontavam que o tratamento clínico (uso de medicamentos orais) e o endovascular / cirúrgico eram similares, ou seja, tinham resultados de recorrência de eventos semelhantes. Em Maio de 2013, foram publicados dois estudos importantes, o PCI e o RESPECT. Este último, particularmente, mostrou uma tendência de melhor evolução dos doentes com AVC indeterminado quando tinham o seu FOP fechado por via endovascular com a prótese denominada AMPLATZER. Esta tendência foi maior ainda em casos de pacientes mais jovens e com FOPs com shunts maiores. Por este motivo, a maioria dos pacientes que tiverem um AVCi de causa indeterminada com o diagnóstico de FOP devem ter uma investigação extensa para investigar outras causas de AVC. Uma vez que seja identificado apenas o FOP, é importante determinar o risco deste, seu tamanho, anatomia, quantidade de shunt (comunicação arterio-venosa) presente, para avaliar se estamos diante de um caso com indicação de fechamento, ou apenas acompanhar e tratar com remédios orais.

O fechamento de FOP em pacientes com esta condição (AVCi), usando cirurgia ou com próteses endovasculares (via cateterismo) pode ser indicado com FOPs grandes, FOP associado a aneurisma, em casos de recorrência (2 ou mais eventos de AVCi), quando o tratamento clínico falhou em prevenir tais eventos. Mesmo nessas situações existem controvérsias na indicação do fechamento do FOP sendo uma conduta a ser norteada pela decisão do paciente e equipe especializada.