Atrial fibrillation: inflammation in disguise?

Atrial fibrillation is highly prevalent, and affected patients are at an increased risk of a number of complications, including heart failure and thrombo-embolism. Over the past years, there has been increasing interest in the role of inflammatory processes in atrial fibrillation, from the first occurrence of the arrhythmia to dreaded complications such as strokes or peripheral emboli. As the standard drug combination which aims at rate control and anticoagulation only offers partial protection against complications, newer agents are needed to optimize treatment. In this paper, we review recent knowledge regarding the impact of inflammation on the occurrence, recurrence, perpetuation and complications of the arrhythmia, as well as the role of anti-inflammatory therapies in the treatment for the disease.

On-line electrical impedance measurement for monitoring blood viscosity during on-pump heart surgery.

BACKGROUND: The viscosity of blood (eta) as well as its electrical impedance at 20 kHz at high shear rate depends on hematocrit, temperature, concentration of macromolecules and red cell deformability. The aim of our study was to investigate the relation between viscosity and electrical impedance in a heart-lung machine-like set-up, because during on-pump heart surgery considerable viscosity changes occur. METHODS: Blood of 10 healthy volunteers was examined under temperature variation between 18.5 and 37 degrees C at four different levels of hemodilution. Blood viscosity was examined with a golden-standard technique, i.e. a Contraves LS 30 Couette viscometer, and the results were compared with measurements of the electrical resistivity (R) at 20 kHz by a specially designed device in series with the tubing system of a heart-lung machine. All measurements were performed at a shear rate of 87 s(-1). RESULTS: Using stepwise multiparameter regression analysis (SPSS) a highly significant correlation was found (r(2) = 0.882) between viscosity (eta) and resistivity (R). Adding the variables sodium ([Na(+)]) and fibrinogen ([Fibr]) concentration the coefficient of correlation further improved to r(2) = 0.928 and the relation became: eta = -0.6844 + 0.038 R + 0.038 [Na(+)] + 0.514 [Fibr]. All coefficients showed a statistical significance of p < 0. 001. CONCLUSIONS: Electrical impedance measurement is feasible in a heart-lung machine-like set-up and allows accurate continuous on-line estimation of blood viscosity; it may offer an adequate way to record and control viscosity changes during on-pump heart surgery.

The impact of maternal plasma volume expansion and antihypertensive treatment with intravenous dihydralazine on fetal and maternal hemodynamics during pre-eclampsia: a clinical, echo-Doppler and viscometric study.

OBJECTIVES: To establish the effects of plasma volume expansion (PVE) followed by intravenous dihydralazine (DH) administration on maternal whole blood viscosity (WBV) and hematocrit, uteroplacental and fetoplacental downstream impedance and umbilical venous (UV) volume flow in pre-eclampsia. METHODS: In 13 pre-eclamptic women maternal and fetal hemodynamics were established by means of combined measurement of maternal arterial blood pressure (BP), WBV, hematocrit and uterine artery (UtA) resistance index (RI) in addition to umbilical artery (UA) pulsatility index (PI) and UV volume flow obtained from UV vessel area and UV time-averaged flow velocity. In each woman all parameters were measured four times at baseline, after PVE, after DH and 24 h after the start of treatment. RESULTS: Maternal diastolic BP, hematocrit and WBV display a significant reduction after PVE. In the fetus UA PI decreases significantly whereas a significant increase in UV cross-sectional area was detected. After maternal DH administration, arterial systolic and diastolic BP and UA PI show a significant decrease compared with the measurements following PVE. At 24 h, only maternal systolic and diastolic BP display a significant further decrease. No significant changes were established for the UtA RI, UV time-averaged velocity and UV volume flow during the entire study period. CONCLUSIONS: During pre-eclampsia, maternal PVE followed by DH administration results in a significant reduction in maternal diastolic BP, maternal hematocrit and WBV. Maternal PVE is associated with a significant increase in UV cross-sectional area and a non-significant rise of 11% in UV volume flow. Maternal DH administration does not result in any change in UV cross-sectional area. However, UA PI decreases significantly after both PVE and DH treatment.

The clinical significance of whole blood viscosity in (cardio)vascular medicine.

Whole blood is a non-Newtonian fluid, which means that its viscosity depends on shear rate. At low shear, blood cells aggregate, which induces a sharp increase in viscosity, whereas at higher shear blood cells disaggregate, deform and align in the direction of flow. Other important determinants of blood viscosity are the haematocrit, the presence of macro-molecules in the medium, temperature and, especially at high shear, the deformability of red blood cells. At the sites of severe atherosclerotic obstructions or at vasospastic locations, when change of vessel diameter is limited, blood viscosity contributes to stenotic resistance thereby jeopardising tissue perfusion. However, blood viscosity plays its most important role in the microcirculation where it contributes significantly to peripheral resistance and may cause sludging in the postcapillary venules. Apart from the direct haemodynamic significance, an increase in blood viscosity at low shear by red blood cell aggregation is also associated with increased thrombotic risk, as has been demonstrated in atrial fibrillation. Furthermore, as increased red blood cell aggregation is a reflection of inflammation, hyperviscosity has been shown to be a marker of inflammatory activity. Thus, because of its potential role in haemodynamics, thrombosis and inflammation, determination of whole blood viscosity could provide useful information for diagnostics and therapy of (cardio)vascular disease.

Prospective study of early discharge after acute myocardial infarction (SHORT)

AIMS: To identify, without additional investigation, a large group of myocardial infarction patients at low risk who would qualify for early discharge. METHODS: The decision rule was developed in 647 unselected patients with consecutively admitted myocardial infarction, and validated in 825 others. Daily event-rates were calculated for major (death, ventricular fibrillation, recurrent infarction, heart failure, advanced AV-block) and minor (unstable angina and rhythm-abnormalities) cardiac complications. RESULTS: Patients free from major complications until day 7 (44% of all patients) were found to constitute a very low risk group and thus would qualify for discharge at day 7. Of the 39% of patients with an uncomplicated infarction (low risk) in the validation group, 31% were discharged at day 7, while 8% stayed longer because of non-cardiac co-morbidity, for social reasons or logistic problems. No major adverse event occurred within 7 days after hospital discharge and only 1.8% developed complications within 1 month. The median duration of hospital stay for all in-hospital survivors was 7 days compared to 10 days in the control group. CONCLUSION: Prospective application of the early discharge decision rule, based upon simple clinical variables and without the need for additional non-invasive and/or invasive tests, resulted in a significant reduction of hospital stay. The decision rule correctly classified patients into high and low risk groups and appeared feasible and safe. Its efficacy was demonstrated by its ability to identify a large group of post infarction survivors at low risk for complications during follow-up.

Modification of physical activity 5 months after myocardial infarction: relevance of biographic and personality characteristics.

The relation between modification of physical activity, a risk factor for coronary heart disease, and personality characteristics was assessed in 166 survivors of a first myocardial infarction (MI). Physical activity was assessed before MI in retrospect and again 5 months after MI. Patients were divided into 3 categories according to their current daily-life physical activities: less active than before MI (n=24), equally active as before MI (n=82), or more active than before MI (n=60). A significant differentiation was found between patients who became less physically active than before MI and the other 2 categories. This less active category was characterized by feelings of disability, a low level of vigor, and feelings of anxiety. In addition, this patient group was on average older and more often female. The results were adjusted for participation in a cardiac rehabilitation program. Finally, the discussion recommends involving psychological intervention in the exercise program for the less active category of patients to diminish feelings of anxiety and disability and to improve vigor.

Modification of smoking habits five months after myocardial infarction: relationship with personality characteristics.

The relationship between personality characteristics and spontaneous modification of smoking habits was assessed in 164 patients after their first myocardial infarction (MI). Smoking habits before the MI were investigated in retrospect and 5 months later. Smoking appeared to have decreased significantly. Persistent smokers could be differentiated from nonsmokers and exsmokers by a significantly high level of state-anxiety and depression. Young persistent smokers had a high level of depression; elderly persistent smokers were highly anxious and had a low level of somatization. The relationship between smoking behaviour modification and personality characteristics is discussed in association with intervention programmes.

Transthoracic echo/Doppler in the identification of patients with chronic non-valvular atrial fibrillation at risk for thromboembolic events.

UNLABELLED: Left atrial spontaneous echo contrast, detected by transoesophageal echocardiography in patients with non-valvular atrial fibrillation reflects slow blood flow and is associated with an increased risk of cardio-embolism. The purpose of this study was to find echo/Doppler predictors of left atrial spontaneous echo contrast by transthoracic examination. In a retrospective case control study, 17 patients with chronic non-valvular atrial fibrillation who had suffered a recent cerebral ischaemic event (group A) and 17 patients with chronic non-valvular atrial fibrillation who had not suffered such an event (group B) were studied. Both groups were matched for age and sex. All patients underwent standard transthoracic echocardiography with transmitral Doppler as well as transoesophageal echocardiography. Left atrial spontaneous echo contrast was demonstrated by transoesophageal echocardiography in nine group A patients and in two group B patients (P = 0.028); left atrial spontaneous echo contrast was not detected by transthoracic echocardiography in these patients. All patients with left atrial spontaneous echo contrast (11 patients) had a left atrial size, corrected for base index, exceeding 24 mm and a transmitral time velocity integral < 10 cm (sensitivity 100%). Left atrial spontaneous echo contrast was absent in six patients with both characteristics (specificity 74%). CONCLUSION: transthoracic echo/Doppler aids in the prediction of the presence of left atrial spontaneous echo contrast and the identification of patients with non-valvular atrial fibrillation with increased cardioembolic risk, thus avoiding transoesophageal echocardiography.

Predictive value of clinical history and electrocardiogram in patients with transient ischemic attack or minor ischemic stroke for subsequent cardiac and cerebral ischemic events. The Dutch TIA Trial Study Group.

OBJECTIVE: Patients with cerebral ischemia have a high mortality rate. The most common cause of death is myocardial infarction. We attempted to identify risk factors for subsequent cardiac events in patients with cerebral ischemia by means of the history and electrocardiography performed with the patient at rest. DESIGN: The original inception cohort was entered in a multicenter randomized clinical trial (30 or 283 mg/d of aspirin) and followed up prospectively for a mean period of 2.6 years. SETTING: Patients were admitted to the hospital or seen in outpatient clinics. PATIENTS: Patients with one or more transient ischemic attacks (symptoms completely reversible within 24 hours) and patients with minor ischemic stroke (symptoms persisting for longer than 24 hours) were randomized, provided they were independent in most activities of daily living. Patients with a definite or probable source of embolism in the heart were excluded. A total of 3021 patients were included in the study. Follow-up was performed at 4-month intervals. MAIN OUTCOME MEASURES: Primary cardiac outcome events were defined as nonfatal myocardial infarction and cardiac death. Cardiac death included sudden death, fatal myocardial infarction, or death due to congestive heart failure; 189 patients suffered a cardiac death--82 of which were sudden deaths--or nonfatal myocardial infarction. RESULTS: By means of multivariate analysis, the following independent predictors for cardiac events were identified (hazards ratio/95% confidence limits): age older than 65 years (1.6/1.2 to 2.2), male sex (1.5/1.1 to 2.1), angina pectoris (1.5/1.0 to 2.3), diabetes (1.6/1.1 to 2.5), anterior infarction noted on electrocardiography (1.7/1.1 to 2.7), inverted T wave noted on the electrocardiogram (1.6/1.1 to 2.4), and left ventricular hypertrophy noted on electrocardiography (3.2/2.0 to 4.9). CONCLUSIONS: The history and the electrocardiogram obtained with the patient at rest are valuable tools for cardiac risk assessment in patients with recent cerebral ischemia.

Risk of cardiac events in atypical transient ischaemic attack or minor stroke. The Dutch TIA Study Group.

Proposed guidelines for the diagnosis of transient ischaemic attack (TIA) involve interpretation of symptoms, so it can be very difficult to distinguish a TIA from other disorders, such as migraine, epilepsy, syncope, or neurosis. Atypical cerebral and visual events may be classified as TIA. To see whether TIA or stroke patients with atypical cerebral or visual symptoms are at high or low risk of cardiac complications, we prospectively followed 572 patients (entered into the Dutch multicentre TIA trial) with a diagnosis of TIA or minor ischaemic stroke, but whose symptoms did not fully accord with internationally accepted criteria. We compared their outcome with that of 2555 other TIA or stroke patients in the trial, who had unequivocal symptoms; all patients were treated with aspirin. During mean follow-up of 2.6 years the risk of a major vascular event did not differ between the groups (14.5% in patients with atypical symptoms vs 15.1% of patients with typical attacks). Patients with atypical attacks had a lower risk of stroke (5.6% vs 9.4%, hazard ratio 0.6, 95% confidence interval 0.4-0.9) and a higher risk of a major cardiac event (8.4% vs 5.9%, 1.4, 1.0-2.0) than did patients with typical attacks. These differences could not be explained by differences in cardiac risk factors, and were independent of minor discrepancies in baseline characteristics between the groups. A heavy or tired feeling in one or two limbs was the only atypical symptom associated with cerebral rather than cardiac events (ratio cardiac/cerebral events 0.8). For all other atypical symptoms cardiac events were about twice as common as cerebral events (range 1.3-2.5). Our findings suggest that TIA or minor stroke patients with atypical symptoms may have symptomatic heart disease, especially cardiac arrhythmia.

'Atypical TIAs' may herald cardiac rather than cerebral events.

Sixty-four patients with atypical transient cerebral or visual symptoms that could not be classified as unequivocal TIAs nor as migraine, epilepsy or neurosis, were followed up for a mean of 3.75 years (range 11 months and 9 years, 240 patient years). Their mean age was 55 years. Only two patients suffered a (non-disabling) stroke, but eight patients had a major cardiac event: fatal myocardial infarction in three, sudden death in one and non-fatal myocardial infarction in four patients. Seven of these eight patients were known to have cardiovascular risk factors. Visual symptoms were relatively benign with regard to cardiac events (2 events in 28 patients), whereas dizziness alone and focal sensory symptoms alone were more strongly associated with subsequent cardiac complications (2 out of 4, and 4 out of 13 patients, respectively). In a control group of 185 patients with 'typical' TIAs or minor strokes, followed for a total of 233 patient years, seven patients had a ischaemic stroke, and only one a cardiac event. Our results suggest that patients with atypical transient cerebral deficits and cardiovascular risk factors may carry a low risk of subsequent stroke, but a high risk of major cardiac events.