| 1. |
- Lönnerholm, Gudmar, et al.
(författare)
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In vitro cellular drug sensitivity at diagnosis is correlated to minimal residual disease at end of induction therapy in childhood acute lymphoblastic leukemia.
- 2009
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Ingår i: Leukemia research. - Oxford : Elsevier BV. - 0145-2126 .- 1873-5835. ; 33:1, s. 46-53
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Tidskriftsartikel (refereegranskat)abstract
- Leukemic cells from 85 children with newly diagnosed precursor B-lineage ALL were tested for in vitro drug sensitivity to a panel of anti-cancer drugs. Minimal residual disease (MRD) was measured by RQ-PCR. There was a significant correlation between MRD day 29 and in vitro sensitivity to prednisolone (p<0.001) and doxorubicin (p=0.017), drugs administered during induction therapy. In patients with t(12;21) (n=20), in vitro sensitivity to doxorubicin was an independent factor for MRD <0.1% (p=0.031; R(2)=0.66). Thus, data show that in vitro drug sensitivity at diagnosis is correlated to cell kill during induction therapy as measured by MRD day 29.
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| 2. |
- Thörn, Ingrid, 1957-, et al.
(författare)
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Minimal residual disease assessment in childhood acute lymphoblastic leukemia : Results of a Swedish multi-centre study comparing real-time PCR and multi-colour flow cytometry
- 2009
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- In this Swedish multi-center study of early treatment response in childhood acute lymphoblastic leukemia (ALL), we evaluated the concordance between multicolour flow cytometry (FCM) and real-time quantitative polymerase chain reaction (RQ-PCR) for assessment of minimal residual disease (MRD). Multiple time points (i.e. day 15, 29, 50 and 106) were evaluated with the NOPHO (Nordic Society of Pediatric Hematology and Oncology) ALL 2000 treatment protocol as backbone. During 2002-2006, 334 children were diagnosed with ALL, where 228 had paired samples taken at any of the four time points. With the detection level of 0.1%, the concordance between RQ-PCR and FCM was 90% in the 726 paired samples analyzed. At day 29, the correlation between the methods was greater with MRD levels >0.1% (rs=0.7, p<0.001) than below (rs=0.2, p=0.024). MRD levels higher than 0.1% at day 29 was a significant predictor of higher risk of having a bone marrow relapse. This was true both for BCP ALL and T-ALL analysed with either FCM or RQ-PCR, although RQ-PCR was a better discriminator than FCM in T-ALL. However, using the NOPHO ALL 2000 protocol, our data indicate that a higher cut-off value (0.2%) should be applied in BCP ALL when using RQ-PCR as MRD method. In contrast, MRD levels ≥ 0.1%, analysed with either method late during induction therapy, was not a predictor of isolated extramedullary relapse. We therefore conclude that MRD assessment by RQ-PCR based IG/TCR rearrangement and multicolour FCM monitoring can be used as a clinical tool if the aim is to find childhood ALL cases with increased risk of having bone marrow relapses.
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| 3. |
- Thörnerup, Ingrid, et al.
(författare)
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Minimal residual disease assessment in childhood acute lymphoblastic leukaemia: a Swedish multi-centre study comparing real-time polymerase chain reaction and multicolour flow cytometry.
- 2011
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 152:6, s. 743-753
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Tidskriftsartikel (refereegranskat)abstract
- Minimal residual disease (MRD) assessment is a powerful prognostic factor for determining the risk of relapse in childhood acute lymphoblastic leukaemia (ALL). In this Swedish multi-centre study of childhood ALL diagnosed between 2002 and 2006, the MRD levels were analysed in 726 follow-up samples in 228 children using real-time quantitative polymerase chain reaction (RQ-PCR) of rearranged immunoglobulin/T-cell receptor genes and multicolour flow cytometry (FCM). Using an MRD threshold of 0·1%, which was the sensitivity level reached in all analyses, the concordance between RQ-PCR and FCM MRD values at day 29 was 84%. In B-cell precursor ALL, an MRD level of ≥0·1% at day 29 predicted a higher risk of bone marrow relapse (BMR) with both methods, although FCM was a better discriminator. However, considering the higher median MRD values achieved with RQ-PCR, a higher MRD cut-off (≥0·2%) improved the predictive capacity of RQ-PCR. In T-ALL, RQ-PCR was notably superior to FCM in predicting risk of BMR. That notwithstanding, MRD levels of ≥0·1%, detected by either method at day 29, could not predict isolated extramedullary relapse. In conclusion, the concordance between RQ-PCR and FCM was high and hence both methods are valuable clinical tools for identifying childhood ALL cases with increased risk of BMR.
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| 4. |
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| 5. |
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| 6. |
- Blomström-Lundqvist, Carina, et al.
(författare)
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Effect of Catheter Ablation vs Antiarrhythmic Medication on Quality of Life in Patients With Atrial Fibrillation : The CAPTAF Randomized Clinical Trial
- 2019
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Ingår i: JAMIA Journal of the American Medical Informatics Association. - Chicago : American Medical Association (AMA). - 1067-5027 .- 1527-974X .- 0098-7484 .- 1538-3598. ; 321:11, s. 1059-1068
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Quality of life is not a standard primary outcome in ablation trials, even though symptoms drive the indication. OBJECTIVE To assess quality of life with catheter ablation vs antiarrhythmic medication at 12 months in patients with atrial fibrillation. DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial at 4 university hospitals in Sweden and 1 in Finland of 155 patients aged 30-70 years with more than 6 months of atrial fibrillation and treatment failure with 1 antiarrhythmic drug or beta-blocker, with 4-year follow-up. Study dateswere July 2008-September 2017. Major exclusionswere ejection fraction <35%, left atrial diameter > 60 mm, ventricular pacing dependency, and previous ablation. INTERVENTIONS Pulmonary vein isolation ablation (n= 79) or previously untested antiarrhythmic drugs (n= 76). MAIN OUTCOMES AND MEASURES Primary outcomewas the General Health subscale score (Medical Outcomes Study 36-Item Short-Form Health Survey) at baseline and 12 months, assessed unblinded (range, 0 [worst] to 100 [best]). There were 26 secondary outcomes, including atrial fibrillation burden (% of time) from baseline to 12 months, measured by implantable cardiac monitors. The first 3 months were excluded from rhythm analysis. RESULTS Among 155 randomized patients (mean age, 56.1 years; 22.6% women), 97% completed the trial. Of 79 patients randomized to receive ablation, 75 underwent ablation, including 2 who crossed over to medication and 14 who underwent repeated ablation procedures. Of 76 patients randomized to receive antiarrhythmic medication, 74 received it, including 8 who crossed over to ablation and 43 for whom the first drug used failed. General Health score increased from 61.8 to 73.9 points in the ablation group vs 62.7 to 65.4 points in the medication group (between-group difference, 8.9 points; 95% CI, 3.1-14.7; P=.003). Of 26 secondary end points, 5 were analyzed; 2 were null and 2 were statistically significant, including decrease in atrial fibrillation burden (from 24.9% to 5.5% in the ablation group vs 23.3% to 11.5% in the medication group; difference -6.8%[95% CI, -12.9% to -0.7%]; P=.03). Of the Health Survey subscales, 5 of 7 improved significantly. Most common adverse events were urosepsis (5.1%) in the ablation group and atrial tachycardia (3.9%) in the medication group. CONCLUSIONS AND RELEVANCE Among patients with symptomatic atrial fibrillation despite use of antiarrhythmic medication, the improvement in quality of life at 12 months was greater for those treated with catheter ablation compared with antiarrhythmic medication. Although the study was limited by absence of blinding, catheter ablation may offer an advantage for quality of life.
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| 7. |
- Blomström, Per, et al.
(författare)
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Cost effectiveness of cardiac resynchronization therapy in the Nordic region : an analysis based on the CARE-HF trial
- 2008
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Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 10:9, s. 869-877
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The aim of this study was to investigate the cost-effectiveness of cardiac resynchronization therapy (CRT) in Denmark, Finland and Sweden. The analysis was based on the CARE-HF trial, a randomised clinical trial investigating the efficacy of adding CRT (n=409) to optimal pharmacological treatment (n=404) in patients with moderate to severe heart failure with markers of cardiac dyssynchrony. The average follow-up time was 29.4 months. METHODS: The health effects were measured in terms of quality-adjusted life years (QALYs) gained. Data on health care resource consumption from CARE-HF was combined with costs for CRT implantation and hospitalisation from university hospitals in Denmark, Finland and Sweden. Calculations were based on patients' expected life time. The expected device lifetime (6 years) was used for CRT, and no additional gains in clinical effects were assumed after the 6 years. RESULTS: The cost-effectiveness ratio per QALY gained was 4800 euros in Denmark, 3600 euros in Finland and 6700 euros in Sweden. The 95% confidence intervals for the cost per QALY gained varied between a lower limit of 1169 euros in Finland to an upper limit of 17,482 euros in Sweden. These values were all below the threshold for being cost-effective in Denmark, Finland and Sweden. CONCLUSIONS: The study indicates that CRT is a cost-effective treatment in Scandinavian health care settings compared to traditional pharmacological therapy and can therefore be recommended for routine use in patients with moderate to severe heart failure and markers of dyssynchrony.
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| 8. |
- Holmqvist, Fredrik, et al.
(författare)
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A decade of catheter ablation of cardiac arrhythmias in Sweden : ablation practices and outcomes
- 2019
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 40:10, s. 820-830
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Catheter ablation is considered the treatment of choice for many tachyarrhythmias, but convincing 'real-world' data on efficacy and safety are lacking. Using Swedish national registry data, the ablation spectrum, procedural characteristics, as well as ablation efficacy and reported adverse events are reported.Methods and Results: Consecutive patients (≥18 years of age) undergoing catheter ablation in Sweden between 01 January 2006 and 31 December 2015 were included in the study. Follow-up (repeat ablation and vital status) was collected through 31 December 2016. A total of 26 642 patients (57 ± 15 years, 62% men), undergoing a total of 34 428 ablation procedures were included in the study. In total, 4034 accessory pathway/Wolff-Parkinson-White syndrome (12%), 7358 AV-nodal re-entrant tachycardia (21%), 1813 atrial tachycardia (5.2%), 5481 typical atrial flutter (16%), 11 916 atrial fibrillation (AF, 35%), 2415 AV-nodal (7.0%), 581 premature ventricular contraction (PVC, 1.7%), and 964 ventricular tachycardia (VT) ablations (2.8%) were performed. Median follow-up time was 4.7 years (interquartile range 2.7-7.0). The spectrum of treated arrhythmias changed over time, with a gradual increase in AF, VT, and PVC ablation (P < 0.001). Decreasing procedural times and utilization of fluoroscopy with time, were seen for all arrhythmia types. The rates of repeat ablation differed between ablation types, with the highest repeat ablation seen in AF (41% within 3 years). The rate of reported adverse events was low (n = 595, 1.7%). Death in the immediate period following ablation was rare (n = 116, 0.34%).Conclusion: Catheter ablations have shifted towards more complex procedures over the past decade. Fluoroscopy time has markedly decreased and the efficacy of catheter ablation seems to improve for AF.
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| 9. |
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| 10. |
- Lindqvist, C Mårten, et al.
(författare)
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The Mutational Landscape in Pediatric Acute Lymphoblastic Leukemia Deciphered by Whole Genome Sequencing
- 2015
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Ingår i: Human Mutation. - : Hindawi Limited. - 1059-7794 .- 1098-1004. ; 36:1, s. 118-128
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Tidskriftsartikel (refereegranskat)abstract
- Genomic characterization of pediatric acute lymphoblastic leukemia (ALL) has identified distinct patterns of genes and pathways altered in patients with well-defined genetic aberrations. To extend the spectrum of known somatic variants in ALL, we performed whole genome and transcriptome sequencing of three B-cell precursor patients, of which one carried the t(12;21)ETV6-RUNX1 translocation and two lacked a known primary genetic aberration, and one T-ALL patient. We found that each patient had a unique genome, with a combination of well-known and previously undetected genomic aberrations. By targeted sequencing in 168 patients, we identified KMT2D and KIF1B as novel putative driver genes. We also identified a putative regulatory non-coding variant that coincided with overexpression of the growth factor MDK. Our results contribute to an increased understanding of the biological mechanisms that lead to ALL and suggest that regulatory variants may be more important for cancer development than recognized to date. The heterogeneity of the genetic aberrations in ALL renders whole genome sequencing particularly well suited for analysis of somatic variants in both research and diagnostic applications.
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| 11. |
- Lönnerholm, Gudmar, 1941-, et al.
(författare)
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In vitro cellular drug resistance adds prognostic information to other known risk-factors in childhood acute lymphoblastic leukemia
- 2011
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Ingår i: Leukemia Research. - : Elsevier. - 0145-2126 .- 1873-5835. ; 35:4, s. 472-478
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Tidskriftsartikel (refereegranskat)abstract
- Leukemic cells from 230 children with newly diagnosed B-cell precursor ALL were tested for in vitro drug resistance to a panel of anti-cancer drugs. Minimal residual disease (MRD) was measured by RQ-PCR. During follow-up, 24 relapses occurred in the 159 children with MRD <0.1% day 29. The risk of any relapse was correlated to vincristine and doxorubicin resistance, with a relative risk of 3.7 (95% CI 1.3-10.5; p=0.016) for patients resistant to both drugs. There was a significant correlation also for the subgroup with extra-medullary relapses. Our findings indicate that analysis of drug resistance can add prognostic information to other known risk-factors including MRD.
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| 12. |
- Lönnerholm, Gudmar, et al.
(författare)
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Vincristine pharmacokinetics in children with Down syndrome
- 2009
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Ingår i: Pediatric Blood & Cancer. - : Wiley. - 1545-5009 .- 1545-5017. ; 52:1, s. 123-125
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Tidskriftsartikel (refereegranskat)abstract
- Children with Down syndrome (DS), who represent about 2% of childhood acute lymphoblastic leukemia, have inferior prognosis compared to non-DS children. For vincristine (and many other anticancer agents) pharmacokinetic data are scant or missing, and there is considerable uncertainty about the optimal dosing of drugs to patients with DS. We studied vincristine pharmacokinetics on treatment day one in six children with DS and compared to 92 non-DS children. No differences were found. Thus, we found no rationale for dose reduction of vincristine in DS children from a strictly pharmacokinetic point of view.
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| 13. |
- Lönnerholm, Stefan, et al.
(författare)
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A high quality of life is maintained late after Maze III surgery for atrial fibrillation.
- 2009
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Ingår i: European Journal of Cardio-Thoracic Surgery. - : Oxford University Press (OUP). - 1010-7940 .- 1873-734X. ; 36:3, s. 558-562
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cox Maze surgery for atrial fibrillation (AF) has been found to have high efficacy in maintaining sinus rhythm and has been shown to improve quality of life early after surgery, but reports on long-term effects in this respect are lacking. This study was therefore undertaken to evaluate the effect of the Maze procedure on health-related quality of life in the long term. METHODS: Patients with drug-refractory AF undergoing the 'cut and sew' Maze III procedure without any modification were assessed with the SF-36 Health Survey regarding quality of life at baseline and late after surgery. Totally 61 patients, mean age 55 years (range: 29-74 years), were evaluated. At the time of surgery, 34 patients (56%) had paroxysmal or persistent AF and the remainder had permanent AF. RESULTS: At late follow-up, at a mean of 55+/-12 months, 54 patients (89%) were free from AF recurrences and another five patients (8%) had experienced only one or a few AF episodes. All eight scales on the SF-36 Health Survey were significantly improved at long-term follow-up compared to baseline. The quality-of-life improvement was seen both in patients with paroxysmal/persistent AF and in those with permanent AF. At long-term follow-up, the quality-of-life scores were comparable with those of the general population. CONCLUSIONS: The Cox Maze III procedure has good long-term efficacy for rhythm control in patients with medically refractory AF, resulting in a quality-of-life improvement, which is maintained late after surgery.
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| 14. |
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| 15. |
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| 16. |
- Lönnerholm, Stefan, et al.
(författare)
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Efficacy and safety of different energy settings for atrial fibrillation ablation using the duty-cycled radiofrequency ablation catheter (PVAC)
- 2014
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Ingår i: Journal of cardiovascular medicine and cardiology. ; 1, s. 102-
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Tidskriftsartikel (refereegranskat)abstract
- Catheter based pulmonary vein isolation (PVI), is the recommended therapy for drug-refractory atrial fibrillation (AF) [1]. The procedure may be technically challenging, can be time consuming and highly dependent on operators skill. In order to improve the efficacy of PV isolation, shorten the procedure time and learning curve of operators; new specially designed catheters for pulmonary vein isolation have been developed [2-4]. One of these catheters is the Pulmonary Vein Ablation Catheter (PVAC) (Medtronic; Minneapolis, USA), which is a 10-pole circular, over the wire catheter used in combination with a multi-channel, duty-cycled radiofrequency generator (GENius; Medtronic) [2]. The feasibility of the PVAC has been demonstrated in a number of studies and randomized clinical studies have reported similar clinical results compared to point-by-point ablation around the pulmonary veins [2,5-9]. The energy can be delivered in a unipolar or bipolar setting or combined in various ratios. A higher proportion of unipolar energy will give deeper lesions but less energy between the poles possibly leading to non-continuous lines [12]. Although certain energy settings have been recommended for PV isolation there are no randomized studies that have compared the different settings for this purpose. The aim of this study was therefore to compare the efficacy and safety of PV isolation using a 4:1 versus a 2:1 unipolar/bipolar energy setting with the PVAC. Our hypothesis was that the 2:1 setting, delivering more unipolar energy, would result in deeper and more transmural lesions for pulmonary vein isolation leading to fewer applications and thus shorter procedure times.
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| 17. |
- Lönnerholm, Stefan, 1966-
(författare)
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Evaluation of New Non-Pharmacological Therapies for Symptomatic Atrial Fibrillation : With Special Emphasis on the Maze Procedure
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Atrial fibrillation is a common disease. With pharmacological therapy most patients with atrial fibrillation have moderate or little symptoms, but a number of patients have severely symptomatic disease. This study evaluates two new non-pharmacological therapies for atrial fibrillation, the Maze procedure and atrial overdrive pacing.In the patients planned for Maze surgery the quality of life, assessed with the SF-36 questionnaire, was very low before the operation. The quality of life was markedly improved 6 and 12 months after the Maze operation, and was comparable to values of the general Swedish population.In the patients with sinus rhythm before surgery, the atrial size and transport function was assessed with echocardiography, and the autonomic balance was assessed with heart rate variability (HRV). The sizes of both atria were reduced and the transmitral early filling / atrial filling (E/A) ratio was increased at 6 months after the operation compared to before. A progressive increase of the E/A ratio was seen during the 24 months follow-up period, indicating a progressive decline of the left atrial transport function.All components of HRV, including the parameters expressing sympathetic and parasympathetic modulation, were markedly decreased early after the Maze procedure compared to before. Late after the operation all components of HRV were still markedly depressed. This is interpreted as a partial autonomic denervation of the heartSingle-site right atrial overdrive pacing with two different levels of overdriving was compared with no pacing in patients with paroxysmal atrial fibrillation in a cross-over study. Overdrive pacing reduced the median number of episodes of atrial fibrillation with 50% compared to no pacing. There was no difference between medium rate overdrive pacing and high rate overdrive pacing.
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| 18. |
- Lönnerholm, Stefan, et al.
(författare)
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Long-term effects of the maze procedure on atrial size and mechanical function
- 2008
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Ingår i: Annals of Thoracic Surgery. - : Elsevier BV. - 0003-4975 .- 1552-6259. ; 85:3, s. 916-920
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Tidskriftsartikel (refereegranskat)abstract
- Background. The Maze procedure is effective in restoring sinus rhythm, but the extensive procedure may have negative effects on atrial mechanical function. Decreased atrial contractility has been observed early after the Maze procedure. The purpose of this study was to determine the long-term effect of the Maze procedure on atrial size and mechanical function. Methods. Fifty-two patients with symptomatic atrial fibrillation, without structural heart or valvular disease, underwent the Cox Maze III procedure. Atrial size and mechanical function were assessed by echocardiographic examination at baseline and postoperatively at a mean +/- SD of 6 +/- 1 and 56 +/- 12 months. Results. The left atrial area was decreased 6 months after the procedure compared with baseline (mean, 15.4 +/- 3.3 vs 17.6 +/- 3.2 cm(2), p < 0.01). By 56 months, however, the left atrial area had increased compared with the 6-month follow-up (19.5 +/- 3.9 vs 15.4 +/- 3.3 cm(2), p < 0.001), resulting in no difference in left atrial size compared with the baseline values. The left atrial contractility, measured as fractional area change, was significantly reduced at 6 and 56 months of follow-up (0.20 +/- 0.09 and 0.19 +/- 0.07 vs baseline 0.36 +/- 0.09), as was the transmitral A-wave velocity (30 +/- 12 and 28 +/- 8 cm/s vs baseline 40 +/- 15). The same pattern was seen for the right atrium. Conclusions. This study shows that the Maze procedure results in a sustained decrease in atrial contractility. The initial reduction in atrial size is later reversed. These findings contradict late improvements in atrial mechanical function after Maze surgery and may have important implications for the risk of thromboembolic complications.
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| 19. |
- Malmborg, Helena, et al.
(författare)
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A prospective randomised comparison of large-tip cryoablation and 8-mm-tip radiofrequency catheter ablation of atrial flutter
- 2009
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Ingår i: Journal of Interventional Cardiac Electrophysiology. - : Springer Science and Business Media LLC. - 1383-875X .- 1572-8595. ; 24:2, s. 127-31
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Although radiofrequency (RF) energy is routinely used for tricuspid isthmus (TI) ablation, it is often associated with discomfort. The paucity of studies comparing the feasibility and efficacy of cryo- versus RF energy for TI-ablation urged us to conduct a prospective, randomised trial. METHODS: Forty patients with atrial flutter (AFl) were randomised to RF- or cryoenergy for TI-ablation. Perceived pain was scored from 1 to 10 on a Visual Analogue Scale. RESULTS: Significantly lower pain scores were recorded for cryoablation versus RF ablation (0.96 +/- 0.73 versus 4.2 +/- 2.4, p = 0.00004). Cryoablation was associated with significantly longer procedure duration and ablation time (137 +/- 35 versus 111 +/- 29 min, p = 0.016 and 81 +/- 40 versus 48 +/- 30 min, p = 0.007) and lower acute success rate (56% versus 100%, p = 0.001) than RF ablation. The recurrence of AFl was 20% (cryo) versus 15% (RF; p = 0.45) after a mean of 15.1 months follow-up. CONCLUSION: Cryoablation results in significantly less pain and discomfort compared to RF ablation of AFl, which is offset by the significantly lower acute success rate.
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| 20. |
- Malmborg, Helena, et al.
(författare)
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Ablation of atrial fibrillation with cryoballoon or duty-cycled radiofrequency pulmonary vein ablation catheter : a randomized controlled study comparing the clinical outcome and safety; the AF-COR study
- 2013
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Ingår i: Europace. - : Oxford University Press (OUP). - 1099-5129 .- 1532-2092. ; 15:11, s. 1567-1573
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: The urge to facilitate the atrial fibrillation (AF) ablation procedure has led to the development of new ablation catheters specifically designed as 'one-shot tools' for pulmonary vein isolation (PVI). The purpose of this study was to compare the efficacy, safety, and procedure times for two such catheters using different energy sources.METHODS AND RESULTS:One hundred and ten patients, referred for ablation of paroxysmal or persistent AF, were randomized to treatment with either the cryoballoon or the circular multipolar duty-cycled radiofrequency-based pulmonary vein ablation catheter (PVAC). Complete PVI was achieved in 98 vs. 93% patients in the cryoballoon and PVAC group, respectively, with complication rates of 8 vs. 2% (P = 0.2). Complete freedom from AF, without antiarrhythmic drugs, after one single ablation procedure was seen in 46% in the cryoballoon vs. 34% after 12 months (P = 0.2). Procedure times were comparable, but fluoroscopy time was shorter for the cryoballoon (32 ± 16 min) than for the PVAC procedures (47 ± 17 min) (P < 0.001). A significant improvement of quality of life (QoL) and arrhythmia-related symptoms was seen in both groups after ablation.CONCLUSION: Both catheters proved comparably effective and safe in achieving acute PVI, apart from the shorter fluoroscopy times achieved with the cryoballoon. At follow-up, there was no statistically significant difference between the groups regarding freedom from AF and clinical success. The QoL increased to the same levels as for the general Swedish population in both groups.
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| 21. |
- Malmborg, Helena, et al.
(författare)
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Acute and clinical effects of cryoballoon pulmonary vein isolation in patients with symptomatic paroxysmal and persistent atrial fibrillation
- 2008
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Ingår i: Europace. - : Oxford University Press (OUP). - 1099-5129 .- 1532-2092. ; 10:11, s. 1277-1280
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: To assess the acute effects, safety, and clinical outcome of atrial fibrillation (AF) ablation using a cryoballoon catheter. METHODS AND RESULTS: Forty patients with paroxysmal or persistent AF underwent pulmonary vein (PV) isolation with a cryoballoon catheter (Arctic Front, CryoCath). Electrocardiograms were recorded in case of symptomatic AF recurrences, and a 24 h Holter recording was performed at last follow-up. Complete PV isolation was achieved in 39 (91%) of the 43 procedures (56% with the cryoballoon catheter alone, 44% with an additional conventional ryocatheter). The number of balloon applications per procedure was 9.6 +/- 1.6. The PV isolation rate was significantly higher (83.9%) if total vessel occlusions were obtained than if intermediate (63.6%, P = 0.01) or poor occlusions were achieved (38.1%, P = 0.0002). The mean procedure time was 239 +/- 48 min. At follow-up (mean 8.9 +/- 4.6 months), 52.5% of patients were free from arrhythmia-related symptoms and another 17.5% had reduction of arrhythmia-related symptoms. Two cases each of phrenic nerve paralysis and dysphagia occurred. CONCLUSIONS: Cryoballoon PV isolation is a feasible technique with a high acute success rate and comparable clinical outcome to radiofrequency ablation. Although complications were rare, the need for an additional conventional cryocatheter warrants further development of the technique.
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| 22. |
- Malmborg, Helena
(författare)
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Catheter Ablation of Atrial Fibrillation and Atrial Flutter : A Comparison of Cryo and Radiofrequency Techniques
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Atrial fibrillation (AF) and atrial flutter (AFl) are two of the most common arrhythmias encountered in the population. Catheter ablation has emerged as a useful tool in the treatment of these arrhythmias. Although radiofrequency (RF) is the most commonly used energy source for ablation, cryoenergy may have some advantageous properties. The purpose of these studies was to evaluate and compare ablation with novel ablation catheters using either of these energy sources.When used for AFl ablation, cryoenergy was associated with less perceived pain than radiofrequency. However, the acute success rate was significantly lower for cryoablation (56%) compared with RF ablation (100%) in our study.Being one of the first centres to use a new so-called “one-shot” device for pulmonary vein isolation (PVI), the cryoballoon, we described our initial experience with this catheter in 40 patients undergoing AF ablation. A high rate of PVI could be achieved although an additional cryocatheter was needed in 44% of the procedures. Freedom from arrhythmia-related symptoms was seen in 53% after a mean follow-up of 8.9 months.Comparing the cryoballoon and a RF-based device intended for PVI, the pulmonary vein ablation catheter (PVAC), both catheters proved comparably effective (≥93%) and safe in achieving PVI with comparable procedure times. After 12 months only 46% versus 34% (ns) in the cryoballoon- and the PVAC group, respectively, were regarded as free from AF without antiarrhythmic drugs, after one ablation procedure, whereas 60% versus 54% reported clinical success. Quality of life was significantly increased in both groups, to a level comparable with the general Swedish population.We tested the hypothesis that RF ablation would be accompanied by a higher activation of the coagulation and inflammatory systems, measured by biomarkers. Such a difference could not be supported in our study, which showed a comparable response with either technique, even though the cryoballoon caused more pronounced myocardial damage.Two different energy settings with different ratios of bipolar-to-unipolar energy were tested with the PVAC under the hypothesis that ablation with a higher proportion of unipolar energy would require fewer applications in order to achieve PVI. However, this study failed to show any difference between the groups.
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| 23. |
- Malmborg, Helena, et al.
(författare)
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Comparison of effects on coagulation and inflammatory markers using a duty-cycled bipolar and unipolar radiofrequency pulmonary vein ablation catheter vs. a cryoballoon catheter for pulmonary vein isolation
- 2013
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Ingår i: Europace. - : Oxford University Press (OUP). - 1099-5129 .- 1532-2092. ; 15:6, s. 798-804
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Thrombo-embolic events are one of the most feared complications related to atrial fibrillation (AF) ablation. Since radiofrequency (RF) energy is thought to be associated with a higher risk of thrombus formation than cryoenergy, the purpose of this study was to assess if the degree of activation of coagulation and inflammatory markers differed between ablation procedures performed with a cryoballoon catheter vs. a RF energy-based pulmonary vein ablation catheter (PVAC), respectively.METHODS AND RESULTS: Thirty patients referred for AF ablation were randomized to pulmonary vein isolation with either the cryoballoon or the PVAC. Biomarkers were studied for endothelial damage (von Willebrand factor antigen), platelet activation (soluble P-selectin), and coagulation activity [prothrombin fragment 1 + 2 (F1 + 2) and D-dimer] at five different time points during the procedure. Troponin I (Trop I) and C-reactive protein were analysed to reflect myocardial destruction and inflammatory activity. Markers of endothelial damage and platelet activation increased after ablation in both the cryo and the RF group. Similarly, the D-dimer levels increased significantly (P = 0.001) in both groups, whereas the F1 + 2 levels increased after the transseptal puncture only (P = 0.001). The overall activation of the coagulation system was, however, comparable between the groups. The cryoballoon was associated with higher Trop I compared with the PVAC (P < 0.001), but the ratios between biomarkers and Trop I were higher with the PVAC than with the cryoballoon.CONCLUSION:Even though the cryoballoon causes a higher degree of myocardial destruction than the PVAC, markers of coagulation, endothelial damage, and inflammation were comparable between the two techniques.
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| 24. |
- Milani, Lili, et al.
(författare)
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DNA methylation for subtype classification and prediction of treatment outcome in patients with childhood acute lymphoblastic leukemia.
- 2010
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 115:6, s. 1214-25
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Tidskriftsartikel (refereegranskat)abstract
- Despite improvements in the prognosis of childhood acute lymphoblastic leukemia (ALL), subgroups of patients would benefit from alternative treatment approaches. Our aim was to identify genes with DNA methylation profiles that could identify such groups. We determined the methylation levels of 1320 CpG sites in regulatory regions of 416 genes in cells from 401 children diagnosed with ALL. Hierarchical clustering of 300 CpG sites distinguished between T-lineage ALL and B-cell precursor (BCP) ALL and between the main cytogenetic subtypes of BCP ALL. It also stratified patients with high hyperdiploidy and t(12;21) ALL into 2 subgroups with different probability of relapse. By using supervised learning, we constructed multivariate classifiers by external cross-validation procedures. We identified 40 genes that consistently contributed to accurate discrimination between the main subtypes of BCP ALL and gene sets that discriminated between subtypes of ALL and between ALL and controls in pairwise classification analyses. We also identified 20 individual genes with DNA methylation levels that predicted relapse of leukemia. Thus, methylation analysis should be explored as a method to improve stratification of ALL patients. The genes highlighted in our study are not enriched to specific pathways, but the gene expression levels are inversely correlated to the methylation levels.
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| 25. |
- Mörtsell, David, et al.
(författare)
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Acute and long-term efficacy and safety with a single cryoballoon application as compared with the standard dual application strategy : a prospective randomized study using the second-generation cryoballoon for pulmonary vein isolation in patients with symptomatic atrial fibrillation
- 2018
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Ingår i: Europace. - : Oxford University Press (OUP). - 1099-5129 .- 1532-2092. ; 20:10, s. 1598-1605
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Tidskriftsartikel (refereegranskat)abstract
- AimsA single cryoballoon (CB) application per vein for pulmonary vein isolation (PVI) in patients with atrial fibrillation (AF) could save time and was therefore compared to the standard approach of two consecutive CB applications for acute and long-term efficacy and safety.Methods and resultsPatients with symptomatic AF were randomized to a single CB application per vein guided by an Achieve® catheter (Single cryo-arm) or to two CB applications using a standard guidewire (Routine cryo-arm). The primary endpoint was the rate of acute complete PVI. Secondary endpoints were freedom from AF evaluated by electrocardiogram and 7 days Holter at 6 and 12 months, symptoms by Symptom Severity Questionnaires and EHRA score and quality of life (QoL) by EQ5D-5L at 12 months. Among 140 patients included, PVI was achieved in 271 (100%) veins in the Single cryo-arm and in 269/271 (99.3%) veins in the Routine cryo-arm, P = 0.25. The procedure time was shorter in the Single cryo-arm, mean ± standard deviation 99.4 ± 33.3 min vs. 118.4 ± 34.3 min, P = 0.0015. Freedom from AF after one procedure at 12 months did not differ; 73.9.0% (Single cryo) vs. 71.4% (Routine), P = 0.74. Symptoms and QoL did also not differ between the two groups. There was a lower complication rate in the Single cryo-group, 2.9% vs. 12.9%, P = 0.03.ConclusionA single CB application shortens the procedure time without affecting acute or long-term efficacy, as compared to the routine two-application strategy, which with the lower complication rates has important implications when defining standards for PVI.
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