Background and purpose
Current guidelines recommend oral anticoagulation (OAC) for patients with atrial fibrillation (AF) and increased risk of thromboembolic events. The reasons for not using OAC in ...AF patients suffering stroke or transient ischaemic attack (TIA) were assessed.
Methods
This retrospective registry included 3404 patients with previously diagnosed AF who suffered a total of 2955 ischaemic strokes and 895 TIAs during 2003–2012.
Results
A CHA2DS2‐VASc score ≥2 and a CHADS2 score ≥2 was observed in 3590 (93.2%) and in 2784 (72.3%) of the events, respectively. Of the high‐risk patients (CHADS2 ≥2) only 55.1% were on OAC before the onset of stroke or TIA. The most frequently documented reasons for withholding OAC were infrequent paroxysms of AF (14%), previous bleeding episodes (13%) and the patient's decline/independent discontinuation of treatment (9%). Moreover, patients with paroxysmal AF (40% using OAC), previous bleeding (26% using OAC) and alcohol abuse (30% using OAC) were using OAC significantly less often than patients without these characteristics. A significant increase in the proportion of high‐risk patients using OAC from 49% in 2003 to 65% in 2012 was seen.
Conclusions
Underuse of anticoagulation is a common contributor to ischaemic strokes and TIA episodes in patients with AF. Infrequent AF episodes, previous bleeds, patient preference and alcohol abuse were the most common reasons for not using OAC.
Background and purpose
Atrial fibrillation (AF) and significant carotid artery stenosis (CAS) often coexist in patients with acute stroke but whether CAS affects the stroke recurrence rate in ...anticoagulated AF patients is largely unknown. The effect of concomitant CAS on both short‐ and long‐term prognosis after stroke in patients with AF was evaluated.
Methods
The multicentre, retrospective FibStroke registry included AF patients with an ischaemic stroke or transient ischaemic attack (TIA) during 2003–2012. In this sub‐study, 165 AF patients with ischaemic stroke or TIA with significant (>50%) CAS (CAS group) and 734 AF patients without CAS (non‐CAS group) were identified. The median follow‐up time after an index event was 3.5 (interquartile range 3.9) years. Long‐term stroke recurrence rate, 30‐day mortality, CHA2DS2‐VASc score, other risk factors and the use and intensity of anticoagulation were assessed.
Results
The recurrence rate of ischaemic stroke (21.2% vs. 12.7%, P = 0.005, 8.1 vs. 3.6 events per100 follow‐up years) was significantly higher in CAS patients compared to the non‐CAS group despite similar anticoagulation/antithrombotic therapy. CAS patients had higher mean CHA2DS2‐VASc scores than non‐CAS patients (4.3 vs. 3.3, P < 0.001). However, in a multivariate analysis CAS was shown to be an independent risk factor for stroke recurrence (hazard ratio 2.02, 95% confidence interval 1.37–3.01, P = 0.001). The 30‐day all‐cause mortality was significantly higher in CAS patients (7.9% vs. 1.9%, P < 0.001) and CAS was an independent risk factor also for 30‐day mortality (odds ratio 3.34, 95% confidence interval 1.51–7.38, P = 0.003).
Conclusions
In patients with AF, concomitant CAS was an independent risk factor for both long‐term stroke recurrence and 30‐day mortality.
Adenoviral vectors are commonly used in clinical gene therapy. Apart from oncolytic adenoviruses, vector replication is highly undesired as it may pose a safety risk for the treated patient. Thus, ...careful monitoring for the formation of replication-competent adenoviruses (RCA) during vector manufacturing is required. To render adenoviruses replication deficient, their genomic E1 region is deleted. However, it has been known for a long time that during their propagation, some viruses will regain their replication capability by recombination in production cells, most commonly HEK293. Recently developed RCA assays have revealed that many clinical batches contain more RCA than previously assumed and allowed by regulatory authorities. The clinical significance of the higher RCA content has yet to be thoroughly evaluated. In this review, we summarize the biology of adenovirus vectors, their manufacturing methods, and the origins of RCA formed during HEK293-based vector production. Lastly, we share our experience using minimally RCA-positive serotype 5 adenoviral vectors based on observations from our clinical cardiovascular gene therapy studies.
In phase I KAT301 trial, intramyocardial adenovirus-mediated vascular endothelial growth factor -D
(AdVEGF-D) gene therapy (GT) resulted in a significant improvement in myocardial perfusion reserve ...and relieved symptoms in refractory angina patients at 1-year follow-up without major safety concerns. We investigated the long-term safety and efficacy of AdVEGF-D GT. 30 patients (24 in VEGF-D group and 6 blinded, randomized controls) were followed for 8.2 years (range 6.3-10.4 years). Patients were interviewed for the current severity of symptoms (Canadian Cardiovascular Society class, CCS) and perceived benefit from GT. Medical records were reviewed to assess the incidence of major cardiovascular adverse event (MACE) and other predefined safety endpoints. MACE occurred in 15 patients in VEGF-D group and in five patients in control group (21.5 vs. 24.9 per 100 patient-years; hazard ratio 0.97; 95% confidence interval 0.36-2.63; P = 0.95). Mortality and new-onset comorbidity were similar between the groups. Angina symptoms (CCS) were less severe compared to baseline in VEGF-D group (1.9 vs. 2.9; P = 0.006) but not in control group (2.2 vs. 2.6; P = 0.414). Our study indicates that intramyocardial AdVEGF-D GT is safe in the long-term. In addition, the relief of symptoms remained significant during the follow-up.
Interindividual variation in mean leukocyte telomere length (LTL) is associated with cancer and several age-associated diseases. We report here a genome-wide meta-analysis of 37,684 individuals with ...replication of selected variants in an additional 10,739 individuals. We identified seven loci, including five new loci, associated with mean LTL (P < 5 × 10(-8)). Five of the loci contain candidate genes (TERC, TERT, NAF1, OBFC1 and RTEL1) that are known to be involved in telomere biology. Lead SNPs at two loci (TERC and TERT) associate with several cancers and other diseases, including idiopathic pulmonary fibrosis. Moreover, a genetic risk score analysis combining lead variants at all 7 loci in 22,233 coronary artery disease cases and 64,762 controls showed an association of the alleles associated with shorter LTL with increased risk of coronary artery disease (21% (95% confidence interval, 5-35%) per standard deviation in LTL, P = 0.014). Our findings support a causal role of telomere-length variation in some age-related diseases.
We investigated whether mitral valve repair (MVP) is superior to mitral valve replacement (MVR) in terms of survival and quality of life during the long-term follow-up.
One hundred eighty-four ...consecutive patients underwent MVP or MVR for mitral regurgitation with or without concomitant coronary artery bypass grafting. Clinical data were recorded prospectively, and the data for the Nottingham Health Profile quality-of-life analysis was collected cross-sectionally. Propensity score analysis was used for the study group matching.
The mean follow-up time was 7.3 +/- 1.4 years. After adjustment for baseline characteristics by the propensity score method, there was a statistically significant survival benefit for the patients who underwent MVP (p = 0.02). Risk factors for death were preoperative unstable angina pectoris (relative risk ratio, 4.4; 95% confidence interval, 2.2 to 8.8), age older than 60 years (relative risk ratio, 1.1; 95% confidence interval, 1.0 to 1.1), use of mitral prosthesis (relative risk ratio, 2.7; 95% confidence interval, 1.4 to 5.3), preoperative renal insufficiency (relative risk ratio, 1.0; 95% confidence interval, 1.0 to 1.007), and preoperative cerebrovascular disorder (relative risk ratio, 2.7; 95% confidence interval, 1.0 to 5.3). The quality of life of the MVP and MVR groups did not differ from each other, but the MVP and the MVR patients had lower energy and mobility scores than an age- and sex-matched reference population.
Survival is longer after MVP than after MVR. The quality of life of MVP and MVR patients does not differ from each other. In terms of most quality-of-life variables, patients who undergo mitral valve operations cope similarly to an age- and sex-matched reference population. Only the scores reflecting energy and mobility were lower in the patients who were operated on than in the reference population.
We studied the incidence and predictors of permanent pacemaker implantation after tricuspid valve operation and its implications on patient outcome in terms of survival, morbidity, and quality of ...life.
Between 1992 and 2007, 136 consecutive patients underwent tricuspid valve repair or valve replacement with a biologic valve at Kuopio University Hospital. Comprehensive clinical data were recorded prospectively. Data for the Nottingham Health Profile quality of life analysis were collected cross-sectionally.
The mean follow-up time was 7.9 +/- 4.1 years (range, 0.8 to 15.7 years). A pacemaker was implanted in 28 patients (21%); 54% were implanted before hospital discharge. The 10-year survival of patients with a pacemaker was higher (94%) than of patients without a pacemaker (59%; p = 0.050). The need of a pacemaker was related to a significantly higher rate of transient ischemic attacks (30% vs 6%, p = 0.004), strokes (9% vs 4%; p = 0.008), and impaired physical capacity in terms of higher New York Heart Association functional class (p = 0.03) and the quality of life scores describing energy (31 vs 17; p = 0.01) and mobility (32 vs 17; p = 0.005).
The need for pacemaker implantation after tricuspid valve operations was high. Unexpectedly, the life expectancy of the patients who needed a pacemaker postoperatively was higher compared with those who did not. This beneficial effect on mortality was offset by impaired morbidity: patients with a pacemaker experienced a significantly higher rate of thromboembolic complications and impaired quality of life.
Atrial fibrillation is often asymptomatic and intermittent making its detection challenging. A photoplethysmography (PPG) provides a promising option for atrial fibrillation detection. However, the ...shapes of pulse waves vary in atrial fibrillation decreasing pulse and atrial fibrillation detection accuracy. This study evaluated ten robust photoplethysmography features for detection of atrial fibrillation. The study was a national multi-center clinical study in Finland and the data were combined from two broader research projects (NCT03721601, URL:
https://clinicaltrials.gov/ct2/show/NCT03721601
and NCT03753139, URL:
https://clinicaltrials.gov/ct2/show/NCT03753139
). A photoplethysmography signal was recorded with a wrist band. Five pulse interval variability, four amplitude features and a novel autocorrelation-based morphology feature were calculated and evaluated independently as predictors of atrial fibrillation. A multivariate predictor model including only the most significant features was established. The models were 10-fold cross-validated. 359 patients were included in the study (atrial fibrillation
n
= 169, sinus rhythm
n
= 190). The autocorrelation univariate predictor model detected atrial fibrillation with the highest area under receiver operating characteristic curve (AUC) value of 0.982 (sensitivity 95.1%, specificity 93.7%). Autocorrelation was also the most significant individual feature (
p
< 0.00001) in the multivariate predictor model, detecting atrial fibrillation with AUC of 0.993 (sensitivity 96.4%, specificity 96.3%). Our results demonstrated that the autocorrelation independently detects atrial fibrillation reliably without the need of pulse detection. Combining pulse wave morphology-based features such as autocorrelation with information from pulse-interval variability it is possible to detect atrial fibrillation with high accuracy with a commercial wrist band. Photoplethysmography wrist bands accompanied with atrial fibrillation detection algorithms utilizing autocorrelation could provide a computationally very effective and reliable wearable monitoring method in screening of atrial fibrillation.
Introduction: Intravenous vernakalant is a therapeutic option for symptomatic, recent-onset atrial fibrillation (AF). This secondary analysis from the large SPECTRUM study assessed the safety and ...effectiveness of vernakalant when used in the emergency department setting (ED group) or in an inpatient hospital setting (non-ED group). Methods: This post hoc analysis of the international, observational, post-authorization SPECTRUM study included 1,289 and 720 recent-onset AF episodes in adults in the ED and non-ED groups, respectively. Safety endpoints included the evaluation of pre-defined health outcomes of interest (HOIs) and other serious adverse events (SAEs) during vernakalant treatment and during the first 24 h after the last infusion. Effectiveness endpoints comprised the rate of successful vernakalant cardioversion, the time from the start of the vernakalant infusion to cardioversion, and the length of hospital stay. Data were analysed using descriptive statistics. Results: The safety profile of vernakalant was similar in the ED and non-ED groups. In the ED group, 12 pre-defined HOIs were reported in 11 patients (0.9%); all but one occurred within 2 h after start of the first infusion. These events comprised nine significant bradycardia cases, of which one was associated with transient hypotension and three with sinus arrest, and 2 cases of atrial flutter with 1:1 conduction. Five other SAEs were reported. All patients with vernakalant-related events recovered without sequelae. No Torsade de Pointes, ventricular fibrillation, or deaths occurred. Successful cardioversion was reported in 67.8% (95% confidence interval: 65.2–70.4) and 66.4% (62.5–70.1) of episodes, with a median time to conversion of 11.0 and 10.0 min in the ED and non-ED groups, respectively. Patients had a median length of hospital stay of 7.4 h and 17.1 h in the ED and non-ED groups, respectively. Conclusion: Intravenous vernakalant was well tolerated with similar cardioversion rates in patients treated in the ED or non-ED setting and does not require admission to a coronary care unit or intensive care unit. First-line treatment with vernakalant could allow an early discharge in patients with recent-onset AF treated in the ED.
Aims
Atrial fibrillation (AF) is the most common tachyarrhythmia and a significant cause of cardioembolic strokes. Atrial fibrillation is often intermittent and asymptomatic making detection a major ...clinical challenge. We evaluated a photoplethysmography (PPG) wrist band in individual pulse detection in patients with AF and tested the reliability of two commonly used algorithms for AF detection.
Methods and results
A 5-min PPG was recorded from patients with AF or sinus rhythm (SR) with a wrist band and analysed with two AF detection algorithms; AFEvidence and COSEn. Simultaneously registered electrocardiogram served as the golden standard for rhythm analysis and was interpreted by two cardiologists. The study population consisted of 213 (106 AF, 107 SR) patients. The wrist band PPG achieved individual pulse detection with a sensitivity of 91.7 ± 11.2% and a positive predictive value (PPV) of 97.5 ± 4.6% for AF, with a sensitivity of 99.4 ± 1.5% 7.7% (95% confidence interval, 95% CI 5.5% to 9.9%); P < 0.001 and PPV of 98.1 ± 4.1% 0.6% (95% CI −0.6% to 1.7%); P = 0.350 for SR. The pulse detection sensitivity was lower 86.7 ± 13.9% with recent-onset AF (AF duration <48 h, n = 43, 40.6%) as compared to late AF (≥48 h, n = 63, 59.4%) with 95.1 ± 7.2% −8.3% (95% CI −12.9% to −3.7%); P = 0.001. For the detection of AF from the wrist band PPG, the sensitivities were 96.2%/95.3% and specificity 98.1% with two algorithms.
Conclusion
The wrist band PPG enabled accurate algorithm-based detection of AF with two AF detection algorithms and high individual pulse detection. Algorithms allowed accurate detection of AF from the PPG. A PPG wrist band provides an easy solution for AF screening.
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