Clinical manifestations and outcomes of severe warfarin overanticoagulation: from the EWA study.

INTRODUCTION: Severe warfarin overanticoagulation is a risk factor for bleeding, but there is little information on its manifestations, prognosis and factors affecting the outcome. We describe the manifestations and clinical outcomes of severe warfarin overanticoagulation in a large group of patients with atrial fibrillation (AF). MATERIAL AND METHODS: All international normalized ratio (INR) samples (n = 961,431) in the Turku University Hospital region between 2003 and 2015 were screened. A total of 412 AF patients with INR ≥9 were compared to 405 patients with stable warfarin anticoagulation for AF. Electronic patient records were manually reviewed to collect comprehensive data. RESULTS: Of the 412 patients with INR ≥9, bleeding was the primary manifestation in 105 (25.5%). Non-bleeding symptoms were recorded in 165 (40.0%) patients and 142 (34.5%) had no symptoms. A total of 17 (16.2%) patients with a bleed and 67 (21.8%) without bleeding died within 30 days after the event. Intracranial haemorrhage strongly predicted death within 30 days. Other significant predictors were non-bleeding symptoms, active malignancies, recent bleed, history of myocardial infarction, older age, renal dysfunction and a recent treatment episode. CONCLUSIONS: Bleeds are not the major determinant of the poor prognosis in severe overanticoagulation, as coincidental INR ≥9 findings also associate with high mortality. KEY MESSAGES Only a quarter of AF patients with INR ≥9 suffered a bleeding event and the clinical manifestation of INR ≥9 had a significant impact on patient outcome. The 30-day mortality rate in patients with INR ≥9 was high ranging from 9.2 to 32.7%. Several significant predictors of 30-day mortality after INR ≥9 were identified.

Self-detection of atrial fibrillation in an aged population: three-year follow-up of the LietoAF intervention study.

BACKGROUND: Atrial fibrillation (AF) is often asymptomatic and undiagnosed until an ischaemic stroke occurs. An irregular pulse is a key manifestation of AF. We assessed whether pulse self-palpation is feasible in screening of AF. METHODS: Altogether 205 residents of Lieto municipality aged ≥75 years were randomized in 2012 to receive brief education on pulse palpation focusing on evaluating rhythm regularity. Self-detected pulse irregularity and new AF diagnoses were recorded, and the subjects' quality of life and use of health care services were assessed during a three-year follow-up. RESULTS: The subjects' median age was 78.2 [3.8] years, and 89 (43.4%) were men. Overall, 139 (68%) subjects had initial good motivation/capability for regular palpation. At four months, 112 (80.6%) subjects with good and 26 (39.4%) with inadequate motivation/capability palpated their pulse daily. At 12 months, 120 (58.5%) and at 36 months, 69 (33.7%) subjects palpated their pulse at least weekly. During the intervention, 67 (32.7%) subjects reported pulse irregularity. New AF was found in 10 (4.9%) subjects, 7 (70%) of whom had reported pulse irregularity. Pulse irregularity independently predicted new AF, but only one (0.5%) subject with new AF sought undelayed medical attention due to pulse irregularity. Quality of life and number of outpatient clinic visits remained unchanged during follow-up. CONCLUSION: Pulse palpation can be learned also by the elderly, but it is challenging to form a continuing habit. The low persistence of pulse self-palpation limits its value in the screening of AF, and strategies to promote persistence and research on alternative screening methods are needed. TRIAL REGISTRATION: http://www.ClinicalTrials.gov identifier: NCT01721005. The trial was registered retrospectively on October 26, 2012.

Reliability of pulse palpation in the detection of atrial fibrillation in an elderly population.

PURPOSE: Atrial fibrillation (AF) may first present as an ischemic stroke. Pulse palpation is a potential screening method for asymptomatic AF. We aimed to assess the reliability of pulse palpation by the elderly in detecting AF. MATERIALS AND METHODS: After brief information and training session conducted by a nurse, 173 subjects aged ≥75 years were instructed to palpate their pulse regularly for a month. After this, their ability to distinguish sinus rhythm (SR), SR with premature ventricular contractions (PVC) and AF by pulse palpation was assessed using an anatomic human arm model programmable with various rhythms. A control group of 57 healthcare professionals received the same information but not the training. Subjects unable to find the pulse were excluded (25 (14.5%) of the elderly and none in the healthcare group). RESULTS: The median age of the elderly subjects was 78.4 [3.9] years and 98 (56.6%) were women. There were no differences between the elderly and healthcare groups in detecting SR (97.3% vs. 96.5%) or SR with PVCs (74.3% vs. 71.4%), but the elderly subjects identified slow (81.8% vs. 56.1%) and fast AF (91.9% vs. 80.7%) significantly better than the healthcare group. The ability to recognize SR with PVCs by the elderly was independently predicted by previous pulse palpation experience, secondary or higher level of education and one-point increase in MMSE score, while identifying the other rhythms had no predictors. CONCLUSIONS: The elderly can learn to reliably distinguish a normal rhythm after education. Pulse self-palpation may be a useful low-cost method to screen for asymptomatic AF.

Incidence and predictors of excessive warfarin anticoagulation in patients with atrial fibrillation-The EWA study.

Vitamin K antagonist warfarin is widely used in clinical practice and excessive anticoagulation is a well-known complication of this therapy. Little is known about permanent and temporary predictors for severe overanticoagulation. The aim of this study was to investigate the occurrence and predicting factors for episodes with very high (≥9) international normalized ratio (INR) values in warfarin treated patients with atrial fibrillation (AF). Excessive Warfarin Anticoagulation (EWA) study screened all patients (n = 13618) in the Turku University Hospital region with an INR ≥2 between years 2003-2015. Patients using warfarin anticoagulation for AF with very high (≥9) INR values (EWA Group) were identified (n = 412 patients) and their characteristics were compared to a control group (n = 405) of AF patients with stable INR during long-term follow-up. Over 20% (n = 92) of the EWA patients had more than one event of very high INR and in 105 (25.5%) patients EWA led to a bleeding event. Of the several temporary and permanent EWA risk factors observed, strongest were excessive alcohol consumption in 9.6% of patients (OR 24.4, 95% CI 9.9-50.4, p<0.0001) and reduced renal function (OR 15.2, 95% CI 5.67-40.7, p<0.0001). Recent antibiotic or antifungal medication, recent hospitalization or outpatient clinic visit and the first 6 months of warfarin use were the most significant temporary risk factors for EWA. Excessive warfarin anticoagulation can be predicted with several permanent and temporary clinical risk factors, many of which are modifiable.

Beat-to-beat, ambulatory hour-to-hour, and home day-to-day variabilities in blood pressure, pulse pressure, and heart rate in comparison with each other and with target-organ damage.

OBJECTIVE: The objective was to compare beat-to-beat, ambulatory hour-to-hour, and home day-to-day variability in blood pressure (BP), pulse pressure (PP), and heart rate (HR) with each other and with target-organ damage. METHODS: We studied a population-based sample of Finnish adults including 150 healthy participants aged between 35 and 64 years. Variability in BP and HR was assessed using self-measured morning and evening recordings from seven consecutive days and 24-h ambulatory recordings. Frequency domain measures of beat-to-beat BP variability and baroreflex sensitivity were determined from 5-min time series. The study participants underwent clinical examination, a clinical interview, measurement of urine albumin levels, and echocardiographic examination. RESULTS: Home BP/PP variability parameters and low frequency (LF) power of beat-to-beat BP/PP variability were mainly associated with left ventricular mass index (LVMI) in models adjusted for age, sex, and BP/PP level. The associations of LVMI with PP variability parameters were stronger than the corresponding associations with BP parameters. The associations of PP variability parameters with LVMI were stronger in old than in young individuals. Home BP/PP variability parameters were mainly associated with the LF power of beat-to-beat BP/PP variability in models adjusted for age, sex, and beat-to-beat BP/PP level and the associations were stronger in old than in young individuals. Home HR variability parameters and 24-h hour-to-hour HR variability were mainly associated with LF/high-frequency powers of beat-to-beat HR variability. CONCLUSION: Reading-to-reading BP/PP variability parameters and their corresponding beat-to-beat variability parameters are partially connected, possibly to common regulatory mechanisms. Their prognostic significance in relation to cardiovascular outcome needs further investigation.

Self-detection of atrial fibrillation in an aged population: the LietoAF Study.

BACKGROUND: Early detection of atrial fibrillation (AF) in older people is important because AF is often asymptomatic and its first manifestation may be a disabling stroke. The objective of the LietoAF Study is to assess the motivation and capability of older people to learn pulse palpation and continue regular pulse measurements, and whether this self-assessment is helpful in the detection of new AF. DESIGN AND METHOD: The LietoAF Study is an intervention study. A total of 205 people aged ≥75 years were randomly selected to participate in the programme where a trained nurse gave individual education on pulse palpation. At 1 month, the eligible participants came to the first follow-up visit to assess the success of pulse self-monitoring. RESULTS: A total of 139 participants (68%) learned pulse palpation and performed regular measurements during the early follow-up period. The significant independent predictors for learning and motivation were high Mini-Mental State Examination score (>24) (OR 7.5, 95% CI 1.5-37.3, p = 0.014), computer use at home (OR 4.7, 95% CI 1.9-11.5, p = 0.001), independence at daily activities (OR 4.2, 95% CI 1.4-13.6, p = 0.013) and low heart rate (OR 1.04, 95% CI 1.0-1.08, p = 0.037). Education did not cause extra visits to local healthcare centres and did not affect quality of life. Four participants observed a new asymptomatic AF during the 1-month follow-up. CONCLUSION: Active older people are motivated and seem to learn pulse palpation. Our early experience suggests that simple nurse-based education is effective and useful in the early detection of asymptomatic AF.

Comparison of results of coronary artery bypass grafting versus percutaneous coronary intervention in octogenarians.

The aim of the present study was to compare the outcomes after coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) in patients aged ≥80 years. The present analysis included 274 patients who underwent isolated CABG and 393 patients who underwent PCI. The patients undergoing PCI had a greater prevalence of a history of cardiac surgery and recent myocardial infarction and had more frequently undergone emergency revascularization. Patients undergoing CABG had a significantly greater prevalence of 3-vessel coronary artery disease. The unadjusted 30-day mortality rate was 8.8% after CABG and 7.4% after PCI (p = 0.514). However, on multivariate analysis, CABG was associated with a significantly increased risk of 30-day mortality (odds ratio 2.246, 95% confidence interval 1.141 to 4.422). The unadjusted overall intermediate survival was significantly poorer after PCI (at 5 years, CABG 72.2% vs PCI 59.5%, p = 0.004), but this was not confirmed on multivariate analysis. PCI and CABG had similar intermediate survival rates when adjusted for propensity score (p = 0.698), a finding confirmed by the analysis of 130 propensity score-matched pairs (at 5 years, CABG 66.4% vs PCI 58.9%, p = 0.730). In conclusion, the survival of patients aged ≥80 years undergoing CABG is excellent, and the suboptimal survival after PCI seems to be related to the disproportionately greater risk of these patients compared to those undergoing CABG. When adjusted for important clinical variables, PCI and CABG achieved similar intermediate results.

Beat-to-beat oscillations in pulse pressure.

We compared 5-min standard deviations (SD) and frequency domain measures of beat-to-beat pulse pressure (PP) variability with those of RR-interval, systolic (SBP) and diastolic (DBP) blood pressure variabilities, and with cross-spectral baroreflex sensitivity (BRS) in a population-based sample of 150 healthy individuals, aged 35-64 years. Beat-to-beat variability of PP was composed of similar frequency components as the other spectral variabilities, and was closely related to SBP variability. The proportion of high frequency (HF) component from overall variability was higher in PP variability than in SBP and DBP variabilities. The low frequency (LF) component and the SD of beat-to-beat PP correlated inversely with BRS (-0.48 and -0.32, respectively; P<0.001 for both). To test a hypothesis that arterial stiffening is associated with increased beat-to-beat oscillation in PP, we examined associations of beat-to-beat PP variability with risk factors of atherosclerosis, i.e. with age, gender, smoking, blood pressure, body mass index, serum lipids, glucose, insulin and homeostasis model assessment of insulin resistance. The SD of beat-to-beat PP variability correlated with age (0.21, P = 0.010), PP (0.31, P<0.001) and body mass index (0.22, P = 0.008). The LF component of PP variability correlated not only with age (0.17, P = 0.041), PP (0.27, P = 0.001) and body mass index (0.22, P = 0.007), but also with serum insulin (0.17, P = 0.042), homeostasis model assessment of insulin resistance (0.18, P = 0.031) and serum triglycerides (0.16, P = 0.048). Our findings suggest that increased beat-to-beat oscillation of PP reflects arterial stiffening and impaired baroreflex function.

Anxiety and hostility are associated with reduced baroreflex sensitivity and increased beat-to-beat blood pressure variability.

OBJECTIVE: The purpose of this study was to determine whether psychological factors are associated with heart rate variability (HRV), blood pressure variability (BPV), and baroreflex sensitivity (BRS) among healthy middle-aged men and women. METHODS: A population-based sample of 71 men and 79 women (35-64 years of age) was studied. Five-minute supine recordings of ECG and beat-to-beat photoplethysmographic finger systolic arterial pressure and diastolic arterial pressure were obtained during paced breathing. Power spectra were computed using a fast Fourier transform for low-frequency (0.04-0.15 Hz) and high-frequency (0.15-0.40 Hz) powers. BRS was calculated by cross-spectral analysis of R-R interval and systolic arterial pressure variabilities. Psychological factors were evaluated by three self-report questionnaires: the Brief Symptom Inventory, the shortened version of the Spielberger State-Trait Anger Expression Inventory, and the Toronto Alexithymia Scale. RESULTS: Psychological factors were not related to HRV. Anxiety was associated with decreased BRS (p = 0.001) and higher low-frequency (p = 0.002) power of systolic arterial pressure variability. These associations were independent of age, gender, other psychological factors, heart rate, and systolic and diastolic blood pressures. Hostility was an independent correlate of increased low-frequency power of diastolic arterial pressure (p = 0.001) and increased high-frequency power of systolic arterial pressure (p = 0.033) variability. CONCLUSIONS: Anxiety and hostility are related to reduced BRS and increased low-frequency power of BPV. Reduced BRS reflects decreased parasympathetic outflow to the heart and may increase BPV through an increased sympathetic predominance.