The role of cardiologists in stroke prevention and treatment: position paper of the European Society of Cardiology Council on Stroke

Stroke is a vascular disease with cerebral consequences, where the heart is a key player. It is defined as ‘a clinical syndrome typified by rapidly developing signs of focal or global disturbance of cerebral functions, lasting more than 24 h or leading to death, with no apparent causes other than of vascular origin’.1 The incidence of stroke varies between 100–400 per 100 000 per year2 and mortality ranks second after coronary heart disease.3 Beyond mortality stroke is the largest single cause of physical disability in adults, second cause of dementia (after Alzheimer disease), major cause of depression, falls and epilepsy in the elderly. Stroke hence presents a tremendous burden both on patients as well as families and health care systems. Despite decreasing mortality rates in recent years,4 hospitalization numbers are increasing3 and long-term care and secondary prevention of stroke will have to move even more in the focus of clinical and health economic efforts. Most strokes (85%) are ischaemic and 15–20% are haemorrhagic. At least 25% of ischaemic strokes are of definite cardio-embolic origin and about a further 20–25% are of suspected cardiac origin or involvement. Most importantly, stroke is clearly recognized as a preventable disease. Stroke patients tend to have pre-existing cardiovascular comorbidities both diagnosed and not at stroke presentation. It is thus inherently logic, that prevention and treatment is an interdisciplinary challenge and should be carried out ‘hand-in-hand’ by neurologists (experts on the brain and cranial vessels) and cardiologists (experts on the heart and peripheral vessels). Recent advances in the diagnosis and treatment of stroke and also of many conditions predisposing to stroke further underline the need for close cooperation of a wide range of medical specialties: neurology, cardiology, neuroradiology, neurosurgery, vascular surgery, intensive care, diabetology, internal medicine, etc. This article summarizes the views and aims of the recently founded European Society of Cardiology (ESC) Council on Stroke focusing on the role of cardiologists in comprehensive and state of the art stroke treatment, as in, prevention, diagnosis, rehabilitation, and long-term care of stroke. Stroke prevention includes the screening for and active influencing of all known risk factors: hypertension, cardiac disease (including arrhythmias), smoking, obesity/diet/physical inactivity, diabetes mellitus, alcohol, stress/depression (Figure 1, Table 1).5 Environmental and behavioural factors are clearly associated to the risk of stroke and may well contribute to the considerable differences in stroke prevalence numbers with a north–south as well as east–west gradient across Europe. Primary prevention of stroke should be a broad population-wide initiative, where cardiologists (along with other specialists—especially neurologists) may serve as triggers, educators, or facilitators, but otherwise primary prevention is task for the politicians, media, health care providers, primary care physicians, and every individual citizen. It is important to decrease the risk of cardiovascular diseases (including stroke) by increasing physical activity and decreasing sedentarity. The role of cardiologists in stroke prevention ECG, electrocardiogram. The role of cardiologists in stroke prevention ECG, electrocardiogram. Cardiovascular risk factors in primary and secondary prevention of stroke. All risk factors contributing to a primary event may continue to apply for subsequent cerebrovascular events. In addition, CV mechanisms caused by the index stroke may further increase the cardiovascular risk for subsequent strokes. Secondary stroke prevention, by contrast, may rest particularly with the specialist medical health care provider and includes the screening for and both the monitoring and treatment of all risk factors. Optimum preventive measures may only be assured when the etiology of stroke is being investigated and targeted. Cardiovascular causes of stroke pose naturally a high risk of other cardiovascular events and strong efforts to detect and to effectively treat such causes are imperative beyond mere stroke prevention. Notably, 1 year after stroke the cardiac causes are the major causes of mortality in these patients.6 Effective cardiac diagnostic workup after stroke (not just during the subacute post-stroke period) is, however, still lacking in most routine clinical practice despite the general understanding of the heart–brain relationship in stroke. Specialists tend to be over focused on their pre-defined roles. That is, cardiac patients are often at risk of subsequent stroke and vice versa stroke patients are often at risk of myocardial infarction, heart failure, or sudden cardiac death. Information on the antithrombotic, antihypertensive, antiarrhythmic, hypolipidaemic, and other medication administered during hospital stay and prescribed at discharge needs to be shared between neurologists and cardiologists. Unfortunately, in most European health care systems there is no specialized long-term follow-up and care for stroke patients as this is well established for other chronic diseases. In fact, the discharged stroke patients are often referred to their general practitioners (GP) without consulting the other specialty medical care (cardiology or neurology). It may be worthwhile to ask patients about their sleeping habits as sleep-related breathing disorders may be important risk factor for cardiac or vascular diseases including stroke. Secondary stroke prevention should be focused on all risk factors in general, but also focus on the (presumed or proven) aetiology (or predisposing condition) of the stroke in each individual patient. Since ischaemic stroke is just one presentation of arteriosclerotic diseases this event highlights the importance of global assessment of vascular risk and the necessity to promote lifestyle modifications and consequent medical treatment post stroke (Figure 1).7 Despite the fact that asymptomatic coronary artery disease (CAD) is common among stroke survivors,8 incidence of myocardial infarction is low in the 1st year post-stroke,9 and routine screening for CAD is not recommended.10 Stroke patients with previous symptomatic CAD, patients with abnormal cardiac work-up and those with very high-vascular risk (large-vessel atheromatous ischaemic stroke, diabetes mellitus, renal failure, etc) should have a cardiology follow-up. Other risk factors such as hyperlipidaemia, hypertension, diabetes, and vascular diseases may be newly diagnosed at the time of the stroke. Therapeutic measures to target these comorbidities may be commenced during the index hospital stay. However, full therapeutic doses and complete work-up may usually not be achieved during the initial hospitalization and subsequent follow-up and further diagnostic and therapeutic steps might be required to achieve the full potential of secondary preventive strategies. The often complex treatment regimen including medical as well as interventional and behavioural strategies requires interdisciplinary concepts and the need for specialized care. The current understanding of stroke is increasing to realize stroke as a chronic disease and stroke patients as chronic patients requiring continued monitoring and medical care. Patient education is of major importance in this context. Hypertension needs a special focus as it is related to both aetiologic types of stroke (i.e. ischaemic and haemorrhagic) via multiple direct and indirect mechanistic pathways (Figure 2). High blood pressure in the intracranial arteries may contribute to intracranial bleeding particularly at weak spots such as aneurysms and other vascular malformations. All types of ischaemic stroke are strongly correlated to high blood pressure levels. Moreover, hypertension also promotes white matter lesions leading to silent brain infarctions. Detailed functional and psychological testing may reveal that such lesions are in fact not fully silent but account for accumulating functional and cognitive deficits. Indirect effects of hypertension on the brain may further add to the very high risk of stroke in these patients. The high pressure in the left ventricle and the left atrium (always present in patients with very high systemic pressures) contributes to the atrial dilatation, fibrosis, myopathy, and heart failure and thus promotes atrial fibrillation (AF) and clot formation.11 Effective treatment of hypertension is known to substantially decrease the stroke rates.12–14 Multiple pathways of hypertension to account for stroke or brain injury. Therapeutic intervention on blood pressure has clearly to be divided between the acute stroke phase and subsequent post-stroke blood pressure control. In the acute ischaemic stroke higher than normal blood pressure is accepted if not pursued in order to achieve sufficient intracranial perfusion pressure. A cochrane analysis including 26 trials and 17 011 participants could not show that actively lowering blood pressure in the acute phase of stroke improves functional outcome.15 In fact, lowering blood pressure in the 1st hours after ischaemic stroke is harmful. Ideal blood pressure range during acute ischaemic stroke will depend on the stroke subtype and other patient specific comorbidities. Some studies found a U-shaped relation between the admission blood pressure and favourable clinical outcomes, with an optimal systolic blood pressure ranging from 121 to 200 mmHg and diastolic blood pressure ranging from 81 to 110 mmHg. However, elevated in-hospital blood pressure during acute ischaemic stroke has been associated with worse clinical outcomes in a more linear fashion.16 Treatment regimen in patients with established cardiovascular disease needs specific attention and considerate adjustment. Plain withdraw of beta blocking therapy in patients with heart failure or coronary artery disease may cause undesirable rebound effects putting even more strain to the myocardium in the acute condition. After the acute phase hypertension should be targeted as a risk factor for further vascular damage and recurring events. Initiation of antihypertensive therapy within 24 h of stroke is relatively safe. Restarting antihypertensive medications is reasonable after the first 24 h for patients who have pre-existing hypertension and are neurologically stable.17 , 18 No data are available to guide selection of medications for the lowering of blood pressure in the setting of acute ischaemic stroke.16 Atrial fibrillation is known to be associated with increased risk of ischaemic stroke. However, despite the clear pathophysiologic concept of AF to account for clot formation in the left atrium and the cardio-embolic genesis of stroke it is a continued matter of debate whether AF is really the cause of stroke or just a risk marker. Particularly the demonstrated temporal disconnect between AF episodes and the stroke fuel this discussion.19 Increasing awareness of the role of unrecognized AF should accelerate efforts to detect AF before stroke has occurred and institute effective thromboprophylaxis with long-term oral anticoagulants.20 Many studies demonstrated that a longer electrocardiogram (ECG) monitoring leads to a higher detection of paroxysmal AF.21–23 The annual detection rate is between 10 and 15%. This highlights the importance of long-term ECG monitoring for all patients who survived ischaemic stroke with undetermined aetiology. Moreover, there is accumulating evidence that most strokes of undetermined origin are in fact, thromboembolic: recently, the Cryptogenic Stroke and Underlying Atrial Fibrillation (CRYSTAL-AF) and the 30-Day Cardiac Event Monitor Belt for Recording Atrial Fibrillation after a Cerebral Ischemic Event (EMBRACE) trials reported that previously unknown paroxysmal AF can be detected in a significant proportion of cryptogenic strokes.22 , 23 Until today, however is has been shown that long-term ECG monitoring can detect AF. Whether this results in a lower risk of stroke has yet to be proven. Other potential sources of embolism in cryptogenic stroke include the mitral and aortic valves, the left cardiac chambers, proximal cerebral arteries of the aortic arch, and the venous system via paradoxical embolism. Accordingly, a new clinical construct termed embolic stroke of undetermined source (ESUS) was recently introduced by the Cryptogenic Stroke/ESUS International Working Group as a potential therapeutic relevant entity with an indication for anticoagulation.24 Cryptogenic ischaemic strokes (ESUS) comprise about 25% of all ischaemic strokes. Embolic strokes of undetermined source may represent a future indication for anticoagulation.24 This is being tested in ongoing randomized trials. Comprehensive diagnostic approach may rationalize the indications to anticoagulant therapy and maybe also to non-pharmacological measures in secondary stroke prevention. It is important to consider AF in patients at risk (e.g. by palpating the pulse in all patients > 65 years visiting the GP25). Screening of (silent) AF may even be considered at a lower age in the presence of a higher risk (CHA2DS2-VASc ≥ 2 in individuals ≥ 55 years). Although the yield of long term monitoring in higher risk populations certainly will be higher, it is uncertain whether it also is cost-effective. Furthermore, the significance of short AF runs detected during long-term monitoring remains to be established. Valvular disease (including prosthetic valves), congenital heart disease (including patients after surgical repair), patent foramen ovale (PFO), atrial septal aneurysm, infective endocarditis, cardiomyopathies, left ventricular aneurysms, intra-cardiac tumours, and other cardiac pathologies are frequent cause of AF and/or stroke. The highest risk is related to the presence of a prosthetic valve or to rheumatic mitral stenosis. It is less known, that also aortic stenosis and any form of heart failure poses an increased risk of stroke if is accompanied by AF. Patent foramen ovale is discussed later in this text. Early diagnosis of stroke is essential to keep the chance for recovery realistic. Acute stroke is a treatable disease, as long as it is treated as a hyperacute emergency where every minute counts—e.g. similar emergency as to trauma, bleeding, or myocardial infarction (Table 2). Diagnosis of stroke is based on clinical history, neurologic examination and brain imaging and is generally the domain of neurologists and imaging specialists (usually neuro-radiologists). The role of cardiologists in the early diagnosis of stroke (first few hours) is minimal. However, cardiologists should play an important role during the subsequent hours to days, when early recognition of potential underlying and/or associated cardiac disease may contribute to the aetiologic diagnosis of stroke. Especially echocardiography and ECG monitoring are important methods in this respect (Table 2). This plays a critical role in those patients who reach functional recovery after stroke—diagnosis and treatment of underlying heart disease may prevent stroke recurrence. Cardiologists should be therefore part of the stroke interdisciplinary teams in comprehensive stroke centres (usually located in large tertiary hospitals, where all involved specialists are available 24 h a day, 7 days a week) as well as in stroke units.26 As an example, patients with symptomatic intracranial atherothrombosis are at high risk of myocardial infarction within the following months. The role of cardiologists and cardiac diagnostic methods in stroke diagnosis ECG, electrocardiogram. The role of cardiologists and cardiac diagnostic methods in stroke diagnosis ECG, electrocardiogram. The role of cardiologists in the treatment of stroke or underlying pathologies PFO, patent foramen ovale. The role of cardiologists in the treatment of stroke or underlying pathologies PFO, patent foramen ovale. Antithrombotic (i.e. antiplatelet or anticoagulant) treatment should not be used in the acute phase (24 h) of stroke for tPA-treated patients, but it is of utmost importance for secondary prevention after ischaemic stroke. Further studies on determining optimal indications, dosage, timing, and drug selection are needed to better specify in whom antiplatelet therapy should be instituted, in whom anticoagulation therapy is better, when (how many days after stroke) such therapy should be started, etc. Obviously this depends also on the underlying cardiac condition. In general aspirin should be initiated within 24–48 h after uncomplicated ischaemic stroke (if the stroke is of vascular the optimal time for oral (e.g. in has to be The to oral at least one or few days ischaemic or ischaemic to days to ischaemic after stroke or in full no in patients with ischaemic stroke risk of was higher than the in stroke) and therefore should not be , should be used for venous embolism after stroke. regimen used in the acute phase of stroke the risk of of the cerebral and the of the and the of treatment should be the risk of Recent trials in are in of antiplatelet therapy in the first post stroke or for patients with or atheromatous symptomatic the time long-term single antiplatelet therapy with aspirin or remains the of secondary stroke prevention in stroke. The of has a anticoagulation for stroke patients that or by in patients with any of AF is established. In patients with heart failure and by contrast, the on therapy is less increased risk of formation with heart failure, the of anticoagulation is by the increased bleeding Further studies are to the of oral in this more on this matter the to the recently European guide for of the oral that also the of anticoagulation post ischaemic and stroke. The recent advances in interventional treatment of acute established of medical as indication for the treatment of stroke (Figure caused by large within h from , The during that with the of the therapeutic time can be to 24 over of stroke patients are for treatment but future and clinical will have to the full potential of this in cerebral artery of embolic and fully after with It is that after the cerebral artery without any underlying A of from the recent trials that will be in future those include on and as well as patient and general for hospital and for stroke The that the of such need to account for a wide of clinical and Further and interdisciplinary are needed to on the of and with related such as interventional cardiologists with may be for and future trials and interdisciplinary may these and have been for primary stroke prevention the acute phase of stroke) and after ischaemic or strokes methods are effective in future and and effective for patients years for patients to be the the should be within 2 of the after or are by the on The role of in the acute phase of stroke of is not yet well Patent foramen ovale has been as a cause of cryptogenic stroke. Patent foramen ovale is correlated with cryptogenic stroke in patients and when atrial septal is also trials have to to medical treatment, thus initial about this of a for secondary prevention of cryptogenic embolism not in a significant in the risk of embolic events or as with medical In one was to medical therapy in the and with a low rate of associated However, very recently randomized trials on have been during the European Stroke and trials. trials in patients than years with large and atrial septal it that this will be in future have been to the patient of the of neurologists and cardiologists is important to the patients. The role of in of patients who have a risk of stroke medical therapy remains to be The individual patient data evidence that stroke and is in with and trials. The recent advances in the interventional treatment of AF (e.g. have been shown to decrease the risk of AF recurrence. It remains to be whether these may also on the risk of stroke. not the need of anticoagulation in anticoagulation of all patients should be pursued for for patients it should continue many patients with AF are with other and there is on the of these in this trials are needed in these at risk of atrial in rate trials might outcomes in of therapy but this has not yet been The Early treatment of Atrial fibrillation for Stroke prevention and the for Atrial Fibrillation patients to rate or early atrial in cardiovascular and mortality will be available within trials will results as to whether of AF is accompanied by of and these trials for treatment of AF and the between and rate might atrial is as a to anticoagulation for patients very high bleeding those that have intracranial of It might be a future for patients at high risk of stroke with high risk for In studies patients with the but more ischaemic strokes with The role of this has yet to be oral anticoagulant is Other ongoing studies in AF patients with for long term anticoagulation with of care. Cardiologists should be and involved in the prevention, diagnosis, and treatment of stroke (Table The of cardiologists should be to other specialists stroke physicians, to the outcomes of stroke patients and to decrease the risk of stroke among who are at risk for stroke. In (e.g. diagnosis and treatment of diagnostic workup to the cardiac cause of stroke) the role of cardiologists is in other the role of cardiologists is interdisciplinary cooperation may the outcomes of stroke patients and to decrease the burden of stroke in Stroke is a disease that requires the of in and therapeutic workup of patients in order to patients at higher risk causes and relevant comorbidities and treat acute and subacute cardiovascular comprehensive and continued monitoring and treatment of risk factors. Stroke are a major concept of acute stroke care and the of in of stroke may be Stroke patients are chronic patients that continued and and treatment of risk factors and stroke including both neurologic and is the most effective treatment of acute ischaemic stroke when by an is by the is by the is by the Cardiovascular an with of the of Atrial between and in the of AF is by the Council and the of and is by the for Cardiovascular and by the of and The views are those of the and not those of the the the of of the other of