Neurologic Manifestations of Systemic Disease: Cardiology and Pulmonary

Mayurkumar D. Bhakta

Although cardiovascular and pulmonary diseases greatly affect multiple organ systems, the neurologic manifestations are one of the most sensitive markers of pathologic disease. Within the cardiopulmonary-vascular system, neurologic changes can be seen every day by all levels of practitioners. These manifestations may be obvious or subtle, but all are important to recognize because they herald important disease states that may be treatable. This chapter will review the most common cardiac and pulmonary diseases that can cause neurologic sequelae.

CARDIAC DISEASES WITH NEUROLOGIC MANIFESTATIONS

The steadily aging population of the United States commonly suffers from some form of cardiac disease. Several of these common cardiac diseases can cause significant neurologic symptoms and possible disability. Cardiogenic embolism to the central nervous system (CNS) is associated with several conditions of the heart including atrial fibrillation (AF), myocardial infarction, cardiac valvular diseases, mitral annular calcification (MAC), mitral valve prolapse (MVP), cardiac valve replacement, left atrial myxoma, dilated cardiomyopathy, patent foramen ovale (PFO), and endocarditis. The results of embolisms can be varied, from transient ischemic attack (TIA) to large ischemic strokes, but their implications are important for both primary and secondary prevention of insults.

Systemic cardiogenic hypoperfusion commonly first manifests with CNS involvement in the form of delirium. Long periods of hypoperfusion, such as those involved with cardiac surgeries and cardiopulmonary bypass machines (CBPs), can also cause neurologic complications that are usually reversible. As the prevalence of coronary artery disease and valvular disease increases, so too will the incidence of cardiac surgeries and, therefore, neurologic involvement in the perioperative and operative period.

CARDIOEMBOLIC STROKE

The diagnosis of cardioembolic stroke is based on the identification of a potential cardiac source combined with the absence of other causes of stroke with variable consideration of neurologic features (25). It is important to identify cardioembolic stroke as a symptom of underlying cardiac disease. Recognition of the different etiologies of cardioembolic stroke will allow one to correctly risk stratify and properly administer the appropriate treatment because cardioembolic strokes may be preventable. There are a myriad of cardiac disease states that can lead to cardioembolic stroke. These include rhythm disorders (AF, atrial flutter, sick sinus syndrome), valvular disease (endocarditis, prosthetic cardiac valves, etc.), and structural abnormalities (cardiac tumors, PFO, atrial septal aneurysm).

Atrial Fibrillation

AF is the most common sustained cardiac arrhythmia, with estimations that >2 million Americans are currently afflicted (15). In population-based cohorts, 10% of all ischemic strokes are probably caused by AF, and the prevalence sharply increases with age. Nearly one third of patients older than 70 years of age with ischemic stroke have AF, and for those older than 75, AF is the leading cause of ischemic stroke (15). The main mechanism involved in AF-related cardioembolic disease is reduced contractility of the left atrial appendage, favoring stasis and thrombus formation (26). There are likely other underlying mechanisms of atrial thrombus formation given the low risk of stroke in patients with “lone AF” compared with “high-risk” groups in persistent AF, but these are yet to be identified.

The overall rate of ischemic stroke among patients with AF varies widely, ranging from 0.5% per year in patients with lone AF to 12% per year for patients with previous TIAs or strokes (15). Classifying patients with AF as low, moderate, or high risk of cardioembolism is paramount for primary prevention. A recent review of classification schemes identified the single most useful model and termed it the CHADS-2 score (Table 29-1) (18). In this model, the physician assigns 1 point each for the presence of congestive heart failure (CHF), hypertension, age of 75 years or older, and diabetes mellitus. In addition, the patient will be assigned 2 points for prior history of stroke or TIA. The sum of these points will then stratify the patients as being at a low, medium, or high risk. Patients with a score of 0 to 1 are low risk, with annual stroke risk being 1.9% to 2.8% per year, respectively. Intermediate risk is a score of 2 to 3 points, with annual risk being 4.0% to 5.9%. Any score from 4 to 6 is deemed to be high risk, with an annual stroke risk from 8.5% to 18.2%. Based on these scoring criteria, patients in the high-risk group should undergo anticoagulation with vitamin K antagonists, moderate-risk patients’ anticoagulation should be individualized, and low-risk patients could possibly be managed with minimal anticoagulation alone in the form of aspirin.

Table 29-1. CHADS Criteria

Criteria	Description	Score
Congestive heart failure (CHF)	Recent history of CHF exacerbation	1
Hypertension	History of hypertension	1
Age	Age >75	1
Diabetes	History of either type 1 or type 2 diabetes	1
Stroke	Any history of prior cerebrovascular disease	2
Sum		6 or less
From Gage BG, Waterman AD, Shannon W, et al. Validation of clinical classification schemes for predicting stroke: results from the National Registry of Atrial Fibrillation. JAMA. 2001;285:2864-2870.

For many years, patients in AF were cardioverted back to sinus rhythm and placed on antiarrhythmic medications for maintenance of the rhythm. The problem was the toxic effects of the antiarrhythmics on other organ systems. The Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) trial compared mortality in patients who were cardioverted and maintained in sinus rhythm versus rate controlling with adequate anticoagulation. This multicenter study showed that there was no statistical difference in mortality or occurrence of stroke in either category, making rate control with adequate anticoagulation with warfarin a safe choice. The authors of the final publication also recommended anticoagulation in cardioverted patients based on risk stratification schemes.

For moderate- and high-risk patients per the CHADS-2 criteria, warfarin is the first-line therapy, with a target international normalized ratio (INR) of 2.0 to 3.0 (2). Patients who present with a stroke in AF should undergo a thorough evaluation to exclude ipsilateral severe atherosclerotic disease prior to initiation of therapy. If evaluation of stroke patients shows no further disease, anticoagulation with aspirin should be started immediately, and warfarin should be started as soon as the patient is medically stable and the cerebral edema from infarct has resolved (27).

Atrial Flutter

Atrial flutter is not as common of a persistent arrhythmia as AF, and there is no strong evidence to suggest its embolic potential. Studies that have looked at its embolic potential have been confounded by the presence of paroxysmal AF along with the atrial flutter (25). Recommendations in primary prevention of cardioembolic disease secondary to this rhythm are based more on the high prevalence of coexistent AF than the atrial flutter itself. Thus, warfarin adjusted to an INR 2.0 to 3.0 is the current recommendation.

Sick Sinus Syndrome

Sick sinus syndrome, also known as “tachy-brady syndrome,” is characterized by fluctuations in heart rate that vary from pauses to tachycardia and possibly AF. The thromboembolic event rate in sick sinus syndrome is 5% to 10% per year (25). Atrial pacemaker insertion is associated with lower stroke rates but does not eliminate the need for anticoagulation. The need for anticoagulation is likely secondary to the high incidence of recurrent AF. The risk for stroke should be assessed as it would be for AF, and anticoagulation should be tailored as such.

Endocarditis

Infective endocarditis is defined as an infection of the heart valves (native and prosthetic), endothelial surfaces (myocardial and valvular structures), and implanted devices (pacemakers, etc.). This diagnosis should be suspected when patients present with acute onset of high fever, rigors, malaise, and new heart murmur. Headache and mental status changes are also common manifestations.

Embolization of vegetations (i.e., endocardial growths) is the second most frequent complication of endocarditis, with stroke being the commonly observed major consequence of the emboli. Staphylococcus aureus infection is associated with the highest stroke rate. The risk of embolization is higher with vegetations of the mitral valve than the aortic valve (3). Embolization tends to occur most commonly at presentation or within 2 days of initiation of antibiotic therapy (12). Cerebral infarction due to emboli or mycotic aneurysm is the presenting sign of endocarditis in 14% of cases (29). The rate of embolic events decreases from 13 events per 1,000 patient days in the first week to <1.2 events per 1,000 patient days after 2 weeks of therapy with the appropriate antibiotic therapy (28). Given the rapid response to appropriate antibiotic therapy, anticoagulation is not necessary. If patients have mechanical valve endocarditis, anticoagulation should not be interrupted. The expected response to therapeutics requires prompt diagnosis of endocarditis when suspected. The most sensitive and specific method for diagnosing endocarditis was devised by Durak et al. (13) from Duke University Medical Center and is now known simply as the Duke Criteria. These criteria have been recently modified to increase sensitivity and specificity and have now become the standard of diagnosis (Table 29-2) (33).

Table 29-2. The Duke Criteria

Major Criteria	Minor Criteria
Typical micro-organism isolated from two separate blood cultures, or micro-organism isolated from persistently positive blood cultures, or single positive blood culture for Coxiella burnetii (or phase 1 IgG antibody titer to C. burnetii >1:800)	Predisposition to infective endocarditis such as previous history of infective endocarditis, injective drug use, prosthetic heart valve, mitral valve prolapse, cyanotic congenital heart disease, or cardiac lesions creating turbulent flow
Evidence of endocardial involvement such as new valvular regurgitation, intracardiac mass, periannular abscess, or new dehiscence of prosthetic valve	Persistent fever
	Vascular phenomena (embolic disease)
	Immunologic phenomena such as Osler nodes, Roth spots, glomerulonephritis, etc.
	Microbiologic findings of atypical organisms (i.e., HACEK organisms)
HACEK, Haemophilus species, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella species.
From Li JS, Sexton DJ, Mick N, et al. Proposed modifications to the Duke criteria for the diagnosis of infective endocarditis.
Clin Infect Dis. 2000;30:633-638.

Embolization of septic vegetation is not without its sequelae, especially in the CNS. Embolization to an arterial intraluminal space or to the vasa vasorum of the cerebral vessels can lead to mycotic aneurysms. These aneurysms carry the risk of rupture and intracranial and subarachnoid hemorrhage. The symptoms associated with a mycotic aneurysm are those associated with aneurysms and subarachnoid hemorrhages, namely meningeal irritation from either an acute or chronic leak into the CNS. Mycotic aneurysms account for 15% of all neurologic complications of endocarditis (39). If mycotic aneurysms are suspected, magnetic resonance imaging (MRI) is superior to computed tomography (CT) for microabscess and aneurysm detection and should be used whenever possible.

Nonbacterial thrombotic endocarditis (NBTE) is caused by vegetations on the heart valves, without evidence of a causative infectious organism. This syndrome occurs more commonly in older individuals and is often associated with neoplasia, disseminated intravascular coagulation, or chronic illness. The primary neurologic complication of NBTE is embolism, which occurs in approximately 42% of cases (35). Diagnosis of NBTE is often difficult and involves a search for infectious causes first. Treatment is aimed at control of the underlying condition, and anticoagulation is recommended if embolization has occurred (51).

Myocardial Infarction

Cardioembolic stroke occurs in approximately 1% of hospitalized patients with myocardial infarction (8). The types of infarction that carry the highest risk of cardioembolism are transmural, apical, and anterolateral, with an increase in risk in patients with CHF or prior history of embolic stroke. The postulated mechanism is thrombus formation in the akinetic ventricle, followed by secondary embolism. Risk stratification of stroke during the acute phase of myocardial infarction includes both clinical and echocardiographic parameters (Table 29-3) (36). Anticoagulation with full-dose heparin followed by warfarin (INR = 2.0 to 3.0) for up to 3 months is recommended for patients who are at high risk (10). The long-term rate of ischemic stroke after myocardial infarction is 1% to 2% per year in the absence of CHF, and aspirin therapy is advocated. No randomized trial comparing warfarin to aspirin in patients with CHF has been performed to determine the best treatment, but most cardiologists recommend warfarin treatment empirically (34).

Table 29-3. Risk Factors for Nonhemorrhagic Stroke

Baseline patient risk factors for nonhemorrhagic stroke following an acute myocardial infarction
	Older age
	Higher heart rate
	History of stroke or transient ischemic attack
	Diabetes
	Previous angina
	Hypertension
In-hospital characteristics associated with higher risk of nonhemorrhagic stroke following an acute myocardial infarction
	Worse Killip class
	Atrial fibrillation/flutter
	Bypass surgery
	Cardiac catheterization
From Mahaffey K, Granger CH, Sloan M, et al. Risk factors for in-hospital nonhemorrhagic stroke in patients with acute myocardial infarction treated with thrombolysis: results from GUSTO-1. Circulation. 1998;97:757-764.

Cardiac Valvular Disease

Mitral stenosis from rheumatic fever carries an increased risk of cardioembolic stroke, but no good estimates of absolute stroke rates are available. The risk increases at least 5% per year when associated with AF. Although evidence-based data are not available, warfarin therapy (INR = 2.0 to 3.0) for patients with rheumatic heart disease and AF has been recommended, with anticoagulation for patients without AF being less clear (24).

MVP is a common form of valvular disease present in approximately 6% of women and 4% of men (51). It is unclear as to whether MVP truly increases the risk of stroke. A recent study of stroke patients showed that the frequency of MVP (5%) is not increased when compared with control groups (5%) (19). In young patients with MVP, the coexistence of atrial septal aneurysm or PFO has confounded the identification of risk factors associated with stroke. Recommendations for primary prevention are therefore undefined. Patients who suffer a TIA with MVP and no other identifiable cause should be treated with aspirin, whereas those already on aspirin therapy with MVP who have a stroke or recurrent events should be anticoagulated with warfarin (51).

Only gold members can continue reading. Log In or Register to continue