Underlying Cardiomyopathy May Cause Some Cryptogenic Stroke

January 02, 2020

Some patients with an ischemic stroke of unknown origin may have underlying cardiomyopathies that could be detected with cardiac magnetic resonance imaging (MRI), a new study suggests.

"Although rare, cardiomyopathies should be considered as a possible cause of acute ischemic stroke," the authors conclude. "The search for cardiomyopathies should include cardiac MRI when echocardiography is normal but there is a suspicion based on clinical grounds or known echocardiographic diagnostic limitations."

The study is published in the January 7 issue of Neurology.

The researchers, led by Ana Catarina Fonseca, MD, PhD, MPH, Hospital de Santa Maria, Lisbon, Portugal, explain that, currently, most stroke etiologic classifications consider only dilated cardiomyopathy as a possible stroke cause.

However, recent studies that prospectively followed up cohorts of patients with hypertrophic cardiomyopathy, noncompaction cardiomyopathy, and restrictive cardiomyopathy showed that these pathologies are associated with an increased risk of ischemic stroke.

For this study, 132 patients (mean age 68 years) with ischemic stroke of unknown origin (after having had an echocardiogram) underwent cardiac MRI, and 7 patients (5.3%) were identified as having a cardiomyopathy.

Four patients had hypertrophic cardiomyopathy, 2 had restrictive cardiomyopathy, and 1 had noncompaction cardiomyopathy. Six of these patients had been classified after standard evaluation as having undetermined stroke and 1 patient as having cardioembolic stroke (atrial fibrillation).

"We found a higher rate of cardiomyopathy in these patients than in the general population," Fonseca told Medscape Medical News.

"Although the frequency of cardiomyopathies that we found was low, it is similar to the frequency of other stroke causes that are systematically searched in patients with cryptogenic stroke such as migrainous infarction or primary angiitis of the central nervous system," the researchers say.

"I don't think this study alone will be enough to recommend MRI for all patients with a stroke of unknown origin. We probably need a larger study and some cost-effectiveness analysis," Fonseca said.   

"Possibly, if there is a suspicion that there might be a cardiomyopathy, then an MRI could be performed.  For example, if a patient has had a stroke of unknown origin and is relatively young — say 50 to 60 years old — and the ECG shows signs of ventricular hypertrophy, then I would consider an MRI," she suggested.  

"Our study only included Portuguese patients, and as cardiomyopathies occur at different frequencies in different populations, we need a multinational study to confirm these results," she added.  

Fonseca noted that detecting cardiomyopathy could also help decide about ongoing treatment.

"We may consider starting an anticoagulant to reduce the risk of subsequent stroke. While it is not known for sure if an anticoagulant is preferable to an antiplatelet for reducing subsequent stroke risk in patients with a cardiomyopathy, personally I favor use of anticoagulants in these patients, as they can have a higher tendency to produce clots," she commented.

In addition, patients with a cardiomyopathy need to be referred to a cardiologist for follow-up as they have an increased risk of arrhythmias and sudden death, Fonseca added.  

In the Neurology article, the researchers report that patients with hypertrophic cardiomyopathy are known to have a fourfold to sixfold greater likelihood of AF development compared with the general population.

In addition, intracardiac thrombi in patients with cardiac amyloidosis are common, with one analysis of 54 necropsy patients with cardiac amyloidosis showing that 14 (26%) had intracardiac thrombi, the researchers note.  

"The clinical trials that investigated the use of anticoagulation vs antiplatelets in patients with embolic stroke of undetermined stroke found no difference between the 2 treatments," the authors write. "Specific subgroups such as patients with cardiomyopathy in the absence of a diagnosis of AF probably could benefit from anticoagulation for secondary prevention."

"While some investigators recommend long-term prophylactic anticoagulation for all patients with noncompaction cardiomyopathy regardless of whether they have experienced thromboembolic complications and regardless of the degree of left ventricular dysfunction, this is an issue that still lacks consensus," they state, adding that in a retrospective analysis of 144 patients with noncompaction cardiomyopathy, 22 (15%) had an ischemic stroke.

"Another Piece of the ESUS Puzzle"

In an accompanying editorial, Gabriel R. de Freitas, MD, Universidade Federal Fluminense, Niteroi, Brazil, and Claudia Barreira, MD, University of São Paulo, Brazil, note that approximately 9% to 25% of ischemic stroke patients have an embolic stroke of unknown source (ESUS), with an annual stroke recurrence of 4.5% despite antiplatelet therapy.

They note that the most common forms of cardiomyopathy, hypertrophic and dilated cardiomyopathy, have a prevalence of 1 in every 250 to 500 adults. Although cardiomyopathies typically cause ischemic stroke by AF, events in patients without arrhythmias have also been described; these are thought to be as a result of stasis and thrombus formation in the left atrium. Current guidelines do not recommend prophylactic anticoagulation in patients with cardiomyopathies without AF.

The editorialists describe the current study as "pioneering." They say it suggests that cardiomyopathies may go unnoticed during traditional investigations and may cause stroke in patients misclassified as having an undetermined cause, because the diagnosis of the cardiomyopathies required cardiac MRI.

The study "highlights that cardiomyopathies could contribute another, probably small, piece in the ESUS puzzle," they write. "However, the relatively small sample size and the restriction to Portuguese patients are limitations of this work and highlight the need to replicate this study in a larger, multiethnic population," they add.

They point out that other investigators have shown that cardiac MRI can also identify more common changes related to stroke, such as atrial fibrosis, even among those with normal-sized atria on echocardiography.

"Together, these findings lead us to wonder whether cardiac MRI should become a mandatory test in patients with ESUS," they state.

de Freitas and Barreira also note that MRI of the cervical vessels can also identify the other major mechanism of ESUS — intraplaque hemorrhage of vulnerable carotid plaques.

However, they say that formal comparison of MRI with other potentially less expensive methods (such as serum biomarkers and ECG findings) is needed, and before implementation in routine clinical practice, cost-effectiveness will need to be established.

The study was supported by "Fundo de Investigação para a Saúde." Fonseca and the editorialists have disclosed no relevant financial relationships. Other coauthors have disclosed relationships with industry. The full list can be found with the original article.

Neurology. Published in the January 7, 2020 issue. Abstract, Editorial

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