| 1. |
- Allentoft, Morten E., et al.
(author)
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100 ancient genomes show repeated population turnovers in Neolithic Denmark
- 2024
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In: Nature. - 0028-0836 .- 1476-4687. ; 625, s. 329-337
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Journal article (peer-reviewed)abstract
- Major migration events in Holocene Eurasia have been characterized genetically at broad regional scales1–4. However, insights into the population dynamics in the contact zones are hampered by a lack of ancient genomic data sampled at high spatiotemporal resolution5–7. Here, to address this, we analysed shotgun-sequenced genomes from 100 skeletons spanning 7,300 years of the Mesolithic period, Neolithic period and Early Bronze Age in Denmark and integrated these with proxies for diet (13C and 15N content), mobility (87Sr/86Sr ratio) and vegetation cover (pollen). We observe that Danish Mesolithic individuals of the Maglemose, Kongemose and Ertebølle cultures form a distinct genetic cluster related to other Western European hunter-gatherers. Despite shifts in material culture they displayed genetic homogeneity from around 10,500 to 5,900 calibrated years before present, when Neolithic farmers with Anatolian-derived ancestry arrived. Although the Neolithic transition was delayed by more than a millennium relative to Central Europe, it was very abrupt and resulted in a population turnover with limited genetic contribution from local hunter-gatherers. The succeeding Neolithic population, associated with the Funnel Beaker culture, persisted for only about 1,000 years before immigrants with eastern Steppe-derived ancestry arrived. This second and equally rapid population replacement gave rise to the Single Grave culture with an ancestry profile more similar to present-day Danes. In our multiproxy dataset, these major demographic events are manifested as parallel shifts in genotype, phenotype, diet and land use.
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| 2. |
- Allentoft, Morten E., et al.
(author)
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Population genomics of post-glacial western Eurasia
- 2024
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In: Nature. - 0028-0836 .- 1476-4687. ; 625:7994, s. 301-311
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Journal article (peer-reviewed)abstract
- Western Eurasia witnessed several large-scale human migrations during the Holocene1–5. Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes—mainly from the Mesolithic and Neolithic periods—from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a ‘great divide’ genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness decreased in the west from the Neolithic transition onwards, whereas, east of the Urals, relatedness remained high until around 4,000 bp, consistent with the persistence of localized groups of hunter-gatherers. The boundary dissolved when Yamnaya-related ancestry spread across western Eurasia around 5,000 bp, resulting in a second major turnover that reached most parts of Europe within a 1,000-year span. The genetic origin and fate of the Yamnaya have remained elusive, but we show that hunter-gatherers from the Middle Don region contributed ancestry to them. Yamnaya groups later admixed with individuals associated with the Globular Amphora culture before expanding into Europe. Similar turnovers occurred in western Siberia, where we report new genomic data from a ‘Neolithic steppe’ cline spanning the Siberian forest steppe to Lake Baikal. These prehistoric migrations had profound and lasting effects on the genetic diversity of Eurasian populations.
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| 3. |
- De Backer, Ole, et al.
(author)
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Efficacy and safety of the Lotus Valve System for treatment of patients with severe aortic valve stenosis and intermediate surgical risk: Results from the Nordic Lotus-TAVR registry
- 2016
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In: International Journal of Cardiology. - : Elsevier. - 0167-5273 .- 1874-1754. ; 219, s. 92-97
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Journal article (peer-reviewed)abstract
- Background: Transcatheter aortic valve replacement (TAVR) has becomean established therapeutic option for patients with symptomatic, severe aortic valve stenosis (AS) who are ineligible or at high risk for conventional valvular surgery. In Northwestern Europe, the TAVR technology is also increasingly used to treat patients with an intermediate risk profile. Methods and results: The study was designed as an independent Nordic multicenter registry of intermediate risk patients treated with the Lotus Valve System (Boston Scientific, MA, USA; N = 154). Valve Academic Research Consortium (VARC)-defined device success was obtained in 97.4%. A Lotus Valve was successfully implanted in all patients. There was no valve migration, embolization, ectopic valve deployment, or TAV-in-TAV deployment. The VARC-defined combined safety rate at 30 days was 92.2%, with a mortality rate of 1.9% and stroke rate of 3.2%. The clinical efficacy rate after 30 days was 91.6% - only one patient had moderate aortic regurgitation. When considering only those patients in the late experience group (N=79), the combined safety and clinical efficacy rates were 93.7% and 92.4%, respectively. The pacemaker implantation rate was 27.9% - this rate was 12.8% in case of a combined implantation depth amp;lt;4 mm and a device/annulus ratio amp;lt; 1.05. Conclusions: The present study demonstrates the efficacy and safety of the repositionable, retrievable Lotus Valve System in intermediate risk patients with AS. The VARC-defined device success rate was 97.4% with a 30-day patient safety and clinical efficacy rate of more than 90%. Less than moderate aortic regurgitation was obtained in 99.4% of patients. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
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| 4. |
- Eriksson, Peter J, 1959, et al.
(author)
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Transcatheter Intervention for Coarctation of the Aorta A Nordic Population-Based Registry With Long-Term Follow-Up
- 2023
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In: Jacc-Cardiovascular Interventions. - : Elsevier BV. - 1936-8798 .- 1876-7605. ; 16:4, s. 444-453
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Journal article (peer-reviewed)abstract
- BACKGROUND Coarctation of the aorta (CoA), a congenital narrowing of the proximal descending thoracic aorta, is a relatively common form of congenital heart disease. Untreated significant CoA has a major impact on morbidity and mortality. In the past 3 decades, transcatheter intervention (TCI) for CoA has evolved as an alternative to surgery.OBJECTIVES The authors report on all TCIs for CoA performed from 2000 to 2016 in 4 countries covering 25 million inhabitants, with a mean follow-up duration of 6.9 years.METHODS During the study period, 683 interventions were performed on 542 patients.RESULTS The procedural success rate was 88%, with 9% considered partly successful. Complications at the intervention site occurred in 3.5% of interventions and at the access site in 3.5%. There was no in-hospital mortality. During follow-up, TCI for CoA reduced the presence of hypertension significantly from 73% to 34%, but despite this, many patients remained hypertensive and in need of continuous antihypertensive treatment. Moreover, 8% to 9% of patients needed aortic and/or aortic valve surgery during follow-up.CONCLUSIONS TCI for CoA can be performed with a low risk for complications. Lifetime follow-up after TCI for CoA seems warranted. (J Am Coll Cardiol Intv 2023;16:444-453) & COPY; 2023 by the American College of Cardiology Foundation.
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| 5. |
- Ihlberg, Leo, et al.
(author)
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Early clinical outcome of aortic transcatheter valve-in-valve implantation in the Nordic countries
- 2013
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In: Journal of Thoracic and Cardiovascular Surgery. - : Elsevier. - 0022-5223 .- 1097-685X. ; 146:5, s. 1047-1054
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Journal article (peer-reviewed)abstract
- Objective: Transcatheter valve-in-valve implantation has emerged as an option, in addition to reoperative surgical aortic valve replacement, to treat failed biologic heart valve substitutes. However, the clinical experience with this approach is still limited. We report the comprehensive experience of transcatheter valve-in-valve implantation in the Nordic countries from May 2008 to January 2012. less thanbrgreater than less thanbrgreater thanMethods: A total of 45 transcatheter aortic valve-in-valve implantations were performed during the study period in 11 centers. The mean age of the patients was 80.6 years (range, 61-91), 26 were male and 19 were female, and the mean EuroSCORE, EuroSCORE II, and Society of Thoracic Surgeons score was 35.4, 16.3, and 14.6, respectively. The type of failure was stenosis and combined in 58% (mean and peak aortic valve gradient, 77 and 45 mm Hg, respectively) and regurgitation in 42% of cases. The SAPIEN/XT (Edwards LifeSciences, Irvine, Calif) and CoreValve (Medtronic Inc, Minneapolis, Minn) system was used in 33 and 12 cases, respectively. The access route was transapical in 25, transfemoral in 17, transaortic in 2, and subclavian in 1 case. The mean follow-up was 14.4 months. The periprocedural and postoperative outcomes were assessed using the Valve Academic Research Consortium criteria. less thanbrgreater than less thanbrgreater thanResults: No intraprocedural mortality occurred. The technical success rate was 95.6% (1 second valve implantation, 1 conversion to open surgery). The all-cause 30-day mortality was 4.4% (1 cardiac-related and 1 aspiration pneumonia). The major complications within 30 days included stroke in 2.2%, periprocedural myocardial infarction in 4.4%, and major vascular complication in 2.2% of patients. At 1 month, all but 1 patient had either no or mild paravalvular leakage, with a mean and peak valve gradient of 17 mm Hg (range, 4-38) and 30 mm Hg (range, 7-68), respectively. The mean gradient was greater than 20 mm Hg in 17% of patients and remained unchanged at 12 months. The 1-year survival was 88.1%. less thanbrgreater than less thanbrgreater thanConclusions: Transcatheter valve-in-valve implantation is widely performed, albeit in small numbers, in most centers in the Nordic countries. The short-termresults were excellent in this high-risk patient population, demonstrating a low incidence of device-or procedure-related complications. However, a considerable number of patients were left with suboptimal systolic valve performance with unknown long-term effects, warranting close surveillance after transcatheter valve-in-valve implantation.
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| 6. |
- Ahn, Henrik Casimir, et al.
(author)
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Can predilatation in transcatheter aortic valve implantation be omitted? - a prospective randomized study
- 2016
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In: Journal of Cardiothoracic Surgery. - : BIOMED CENTRAL LTD. - 1749-8090. ; 11:124
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Journal article (peer-reviewed)abstract
- Background: The use of a balloon expandable stent valve includes balloon predilatation of the aortic stenosis before valve deployment. The aim of the study was to see whether or not balloon predilatation is necessary in transcatheter aortic valve replacement (TAVI). Methods: Sixty consecutive TAVI patients were randomized to the standard procedure or to a protocol where balloon predilatation was omitted. Results: There were no significant differences between the groups regarding early hemodynamic results or complication rates. Conclusions: TAVI can be performed safely without balloon predilatation and with the same early results as achieved with the standard procedure including balloon predilatation. The reduction in the number of pacing periods required may be beneficial for the patient.
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| 7. |
- Ahn, Henrik Casimir, et al.
(author)
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Transvenous Implantation of a Stent Valve in Patients With Degenerated Mitral Prostheses and Native Mitral Stenosis
- 2016
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In: Annals of Thoracic Surgery. - : Elsevier. - 0003-4975 .- 1552-6259. ; 101:6, s. 2279-2284
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Journal article (peer-reviewed)abstract
- BACKGROUND: The purpose of this study was to report the use of a transvenous transseptal approach using a stent valve in patients with degenerated biological mitral valve prostheses, regurgitation after mitral repair, and native mitral stenosis.METHODS: Ten patients (median age, 74 years; range, 20-89 years; 5 men and 5 women) with degenerated mitral bioprosthetic valves (n = 7), failed mitral repair (n = 1), or calcified native stenotic valves (n = 2) underwent transvenous implantation of a stent valve.RESULTS: The procedure was initially successful in all patients. Predilation was performed for balloon sizing only in the 2 patients with native mitral stenosis. The stent valve was deployed during 1 period of rapid pacing. A guidewire, as a loop from the right femoral vein and through the left ventricular apex, facilitated a good angle and secure positioning of the stent valve. An ultrasonographically guided puncture of the apex was carried out in 6 patients, and in the other 4 we performed a minithoracotomy before apical puncture. All valves were implanted in a good position with improved function and without significant paravalvular leakage (PVL). There were no periprocedural deaths. The 30-day survival was 80% (8 of 10 patients), and 60% (6 of 10) of patients were still alive a median time of 290 days after the procedure.CONCLUSIONS: Transvenous transseptal implantation of a stent valve was performed in 10 patients with mitral valve disease, with good early functional results. These high-risk patients must be carefully selected by a multidisciplinary team because the procedure carries a high mortality.
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| 8. |
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| 9. |
- Appel, Carl-Fredrik, et al.
(author)
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Transcatheter versus surgical treatment for aortic stenosis : Patient selection and early outcome
- 2012
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In: Scandinavian Cardiovascular Journal. - : Informa Healthcare. - 1401-7431 .- 1651-2006. ; 46:5, s. 301-307
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Journal article (peer-reviewed)abstract
- Objectives. To describe short-term clinical and echocardiography outcomes in patients undergoing transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR). To explore patient selection criteria for treatment with TAVI. Design. TAVI patients (n = 45) were matched to SAVR patients (n = 45) with respect to age within +/- 10 years, sex and systolic left ventricular function. Results. TAVI patients were older, 82 +/- 8 versus 78 +/- 5 years (p = 0.005) and they had higher logEuroSCORE, 16 +/- 11% versus 8 +/- 4% (p andlt; 0.001). There were no significant differences in 30 days mortality, stroke and myocardial infarction. TAVI patients received less erythrocyte (53% vs. 78%, p = 0.03) and thrombocyte (7% vs. 27%, p = 0.02) transfusions. Postoperative atrial fibrillation was less common (18% vs. 60%, p andlt; 0.001) in the TAVI group. Paravalvular regurgitation was more common in TAVI patients (87% vs. 0%, p andlt; 0.001) and 27% had access site complications. Aortic transvalvular velocity was 2.3 +/- 0.4 m/s versus 2.6 +/- 0.5 m/s (p = 0.002) and mean valve pressure gradient was 12 +/- 4 mmHg versus 15 +/- 5 mmHg (p = 0.01) in the TAVI and SAVR groups, respectively. Twenty-nine (64%) of the TAVI patients had logEuroSCORE andlt; 15%. Conclusions. Both TAVI and SAVR have good short term clinical outcome with excellent hemodynamic result. In clinical practice, factors other than high logEuroSCORE play an important role in patient selection for TAVI.
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| 10. |
- Baranowski, Jacek, et al.
(author)
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A simplified protocol for transcatheter aortic valve implantation that reduces procedure-related risk
- 2016
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In: Journal of Cardiovascular Diseases & Diagnosis. - : Omics Publishing Group. - 2329-9517. ; 4:3
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Journal article (peer-reviewed)abstract
- Objectives: Transcatheter Aortic Valve Implantation is now a well-established procedure and continuous development has improved the technique. The object of this paper is to describe the successive steps taken at our department to improve our protocol, resulting in a more effective and patient-safe procedure.Design: An echo-guided method for aortic cusp alignment was used in 229 patients. In 139 patients pre-dilatation was excluded from the protocol. In the last 47 of the patients we exchanged the stiff guide-wire in the left ventricle with a soft wire for valve placement.Results: There was a significant decrease in the use of contrast medium during the period with 90% of patients receiving less than 50 ml contrast and 35% no contrast at all. In more than half the patients we only used rapid pacing in association with deployment of the stent valve. We had six cases ofpericardial bleeding due to penetration of the stiff guide wire through the left ventricular (LV) wall. This complication was avoided in all subsequent patients where we exchanged the stiff catheter to a soft guidewire in the ascending aorta before introduction of the wire and stent valve into the LV.Conclusions: We have successively modified our standard protocol for implantation of a balloon-expandable transcatheter aortic valve. This has simplified the procedure and reduced the risk for certain procedure-related complications.
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| 11. |
- Baranowski, Jacek, et al.
(author)
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Echo-guided presentation of the aortic valve minimises contrast exposure in transcatheter valve recipients
- 2011
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In: Catheterization and cardiovascular interventions. - : Wiley. - 1522-1946 .- 1522-726X. ; 77:2, s. 272-275
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Journal article (peer-reviewed)abstract
- OBJECTIVES: We have developed a method using transthoracic echocardiography in establishing optimal visualization of the aortic root, to reduce the amount of contrast medium used in each patient. BACKGROUND: During transcatheter aortic valve implantation, it is necessary to obtain an optimal fluoroscopic projection for deployment of the valve showing the aortic ostium with the three cusps aligned in the beam direction. This may require repeat aortic root angiograms at this stage of the procedure with a high amount of contrast medium with a risk of detrimental influence on renal function. METHODS: We studied the conventional way and an echo guided way to optimize visualisation of the aortic root. Echocardiography was used initially allowing easier alignment of the image intensifier with the transducer's direction. RESULTS: Contrast volumes, radiation/fluoroscopy exposure times, and postoperative creatinine levels were significantly less in patients having the echo-guided orientation of the optimal fluoroscopic angles compared with patients treated with the conventional approach. CONCLUSION: We present a user-friendly echo-guided method to facilitate fluoroscopy adjustment during transcatheter aortic valve implantation. In our series, the amounts of contrast medium and radiation have been significantly reduced, with a concomitant reduction in detrimental effects on renal function in the early postoperative phase.
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| 12. |
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| 13. |
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| 14. |
- Baranowski, Jacek, et al.
(author)
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TAVI without BAV
- 2014
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Conference paper (peer-reviewed)
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| 15. |
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| 16. |
- Berglund, Elisabeth, et al.
(author)
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High incidence of infective endocarditis in adults with congenital ventricular septal defect
- 2016
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In: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 102:22, s. 1835-1839
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Ventricular septal defects (VSDs), if haemodynamically important, are closed whereas small shunts are left without intervention. The long-term prognosis in congenital VSD is good but patients are still at risk for long-term complications. The aim of this study was to clarify the incidence of infective endocarditis (IE) in adults with VSD. METHODS: The Swedish registry for congenital heart disease (SWEDCON) was searched for adults with VSD. 779 patients were identified, 531 with small shunts and 248 who had the VSD previously closed. The National Patient Register was then searched for hospitalisations due to IE in adults during a 10-year period. RESULTS: Sixteen (2%) patients were treated for IE, 6 men and 10 women, with a mean age of 46.3+/-12.2 years. The incidence of IE was 1.7-2.7/1000 years in patients without previous intervention, 20-30 times the risk in the general population. Thirteen had small shunts without previous intervention. There was no mortality in these 13 cases. Two patients had undergone repair of their VSD and also aortic valve replacement before the episode of endocarditis and a third patient with repaired VSD had a bicuspid aortic valve, all of these three patients needed reoperation because of their IE and one patient died. No patient with isolated and operated VSD was diagnosed with IE. CONCLUSIONS: A small unoperated VSD in adults carries a substantially increased risk of IE but is associated with a low risk of mortality.
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| 17. |
- Bjursten, Henrik, et al.
(author)
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Calcium Load in the Aortic Valve, Aortic Root, and Left Ventricular Outflow Tract and the Risk for a Periprocedural Stroke
- 2022
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In: Structural Heart-the Journal of the Heart Team. - : Elsevier BV. - 2474-8706 .- 2474-8714. ; 6:4
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Journal article (peer-reviewed)abstract
- Background: Periprocedural stroke during transcatheter aortic valve implantation is a rare but devastating complication. The calcified aortic valve is the most likely source of the emboli in a periprocedural stroke. The total load and distribution of calcium in the leaflets, aortic root, and left ventricular outflow tract varies from patient to patient. Consequently, there could be patterns of calcification that are associated with a higher risk of stroke. This study aimed to explore whether the pattern of calcification in the left ventricular outflow tract, annulus, aortic valve, and ascending aorta can be used to predict a periprocedural stroke. Methods: Among the 3282 consecutive patients who received a transcatheter aortic valve implantation in the native valve in Sweden from 2014 to 2018, we identified 52 who had a periprocedural stroke. From the same cohort, a control group of 52 patients was constructed by propensity score matching. Both groups had one missing cardiac computed tomography, and 51 stroke and 51 control patients were blindly reviewed by an experienced radiologist. Results: The groups were well balanced in terms of demographics and procedural data. Of the 39 metrics created to describe calcium pattern, only one differed between the groups. The length of calcium protruding above the annulus was 10.6 mm (interquartile range 7-13.6) for patients without stroke and 8 mm (interquartile range 3-10) for stroke patients. Conclusions: This study could not find any pattern of calcification that predisposes for a periprocedural stroke.
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| 18. |
- Bjursten, Henrik, et al.
(author)
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Characteristics and Outcomes of Patients Receiving a Second Rescue Valve During Transcatheter Aortic Valve Implantation
- 2024
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In: Structural Heart. - : Elsevier. - 2474-8706 .- 2474-8714. ; 8:2
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Journal article (peer-reviewed)abstract
- Background: Transcatheter aortic valve implantation (TAVI) has become a safe procedure. However, complications occur, including uncommon complications such as valve malposition, which requires the implantation of an additional rescue valve (rescue-AV). The aim was to study the occurrence and outcomes of rescue-AV in a nationwide registry. Methods: The Swedish national TAVI registry was used as the primary data source, where all 6706 TAVI procedures from 2016 to 2021 were retrieved. Nontransfemoral access and planned valve-in-valve were excluded. In total, 79 patients were identified as having had a rescue-AV, and additional detailed data were collected for these patients. This dataset was analyzed for any characteristics that could predispose patients to a rescue-AV. The outcome of patients receiving rescue-AV also was studied. Results: Of the 5948 patients in the study, 1.3% had a rescue-AV. There were few differences between patients receiving 1 valve and rescue-AV patients. For patients receiving a rescue-AV, the 30-day mortality was 15.2% compared to 1.6% in the control group. A poor outcome after rescue-AV was often associated with a second complication; for example, stroke, need for emergency surgery, or heart failure. Among the patients with rescue-AV who survived at least 30 days, landmark analyses showed similar survival rates compared to the control group. Conclusions: Among TAVI patients in a nationwide register, rescue-AV occurred in 1.3% of patients. The 30-day mortality in patients receiving rescue-AV was high, but long-term outcome among 30-day survivors was similar to the control group.
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| 19. |
- Bjursten, Henrik, et al.
(author)
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Characteristics and Outcomes of Patients Receiving a Second Rescue Valve During Transcatheter Aortic Valve Implantation
- 2024
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In: Structural Heart. - : Elsevier. - 2474-8706 .- 2474-8714. ; 8:2
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Journal article (peer-reviewed)abstract
- BackgroundTranscatheter aortic valve implantation (TAVI) has become a safe procedure. However, complications occur, including uncommon complications such as valve malposition, which requires the implantation of an additional rescue valve (rescue-AV). The aim was to study the occurrence and outcomes of rescue-AV in a nationwide registry.MethodsThe Swedish national TAVI registry was used as the primary data source, where all 6706 TAVI procedures from 2016 to 2021 were retrieved. Nontransfemoral access and planned valve-in-valve were excluded. In total, 79 patients were identified as having had a rescue-AV, and additional detailed data were collected for these patients. This dataset was analyzed for any characteristics that could predispose patients to a rescue-AV. The outcome of patients receiving rescue-AV also was studied.ResultsOf the 5948 patients in the study, 1.3% had a rescue-AV. There were few differences between patients receiving 1 valve and rescue-AV patients. For patients receiving a rescue-AV, the 30-day mortality was 15.2% compared to 1.6% in the control group. A poor outcome after rescue-AV was often associated with a second complication; for example, stroke, need for emergency surgery, or heart failure. Among the patients with rescue-AV who survived at least 30 days, landmark analyses showed similar survival rates compared to the control group.ConclusionsAmong TAVI patients in a nationwide register, rescue-AV occurred in 1.3% of patients. The 30-day mortality in patients receiving rescue-AV was high, but long-term outcome among 30-day survivors was similar to the control group.
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| 20. |
- Droppa, Michal, et al.
(author)
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Risk factors for permanent pacemaker implantation in patients receiving a balloon-expandable transcatheter aortic valve prosthesis
- 2020
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In: Heart and Vessels. - : Springer. - 0910-8327 .- 1615-2573. ; 35, s. 1735-1745
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Journal article (peer-reviewed)abstract
- Permanent pacemaker implantation (PPI) is a widely recognized complication associated with TAVI (incidence up to 20%). Smaller registries have identified several variables associated with PPI. The objective was to validate patient- and transcatheter aortic valve implantation (TAVI)-related procedural variables associated with PPI. We performed a retrospective analysis of patients from six European centers undergoing TAVI with the Edwards SAPIEN 3 prosthesis. Baseline variables and pre-procedural ECG characteristics and CT-scans were taken into account. Data for 1745 patients were collected; 191 (10.9%) required PPI after TAVI. The baseline variables pulmonary hypertension (OR 1.64; 95% CI 1.01-2.59), QRS duration > 117 ms (OR 2.58; 95% CI 1.73-3.84), right bundle branch block (RBBB; OR 5.14; 95% CI 3.39-7.72), left anterior hemi block (OR 1.92; 95% CI 1.19-3.02) and first-degree atrioventricular block (AVB, OR 1.63; 95%CI 1.05-2.46) were significantly associated with PPI. RBBB (OR 8.11; 95% CI 3.19-21.86) and first-degree AVB (OR 2.39; 95% CI 1.18-4.66) remained significantly associated in a multivariate analysis. Procedure-related variables included access site (TF; OR 1.97; 95% CI 1.07-4.05), implanted valve size (29 mm; OR 1.88; 95% CI 1.35-2.59), mean TAVI valve implantation depth below the annulus > 30% (OR 3.75; 95% CI 2.01-6.98). Patients receiving PPI had longer ICU stays and later discharges. Acute kidney injury stage 2/3 was more common in patients with PPI until discharge (15.2 vs. 3.1%;p = 0.007), but was not statistically significant thereafter. Further differences in outcomes at 30 days did not reach significance. The data will aid pre- and post-procedural patient management and prevent adverse long-term outcomes. Clinical Trial: NCT03497611.
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| 21. |
- Edvinsson, B., et al.
(author)
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Does persistent (patent) foramen ovale closure reduce the risk of recurrent decompression sickness in scuba divers?
- 2021
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In: Diving and hyperbaric medicine. - : Diving and Hyperbaric Medicine Journal. - 1833-3516 .- 2209-1491. ; 51:1, s. 63-67
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Journal article (peer-reviewed)abstract
- Introduction: Interatrial communication is associated with an increased risk of decompression sickness (DCS) in scuba diving. It has been proposed that there would be a decreased risk of DCS after closure of the interatrial communication, i.e., persistent (patent) foramen ovale (PFO). However, the clinical evidence supporting this is limited. Methods: Medical records were reviewed to identify Swedish scuba divers with a history of DCS and catheter closure of an interatrial communication. Thereafter, phone interviews were conducted with questions regarding diving and DCS. All Swedish divers who had had catheter-based PFO-closure because of DCS were followed up, assessing post-closure diving habits and recurrent DCS. Results: Nine divers, all with a PFO, were included. Eight were diving post-closure. These divers had performed 6,835 dives (median 410, range 140-2,200) before closure, and 4,708 dives (median 413, range 11-2,000) after closure. Seven cases with mild and 10 with serious DCS symptoms were reported before the PFO closure. One diver with a small residual shunt suffered serious DCS post-closure; however, that dive was performed with a provocative diving profile. Conclusion: Divers with PFO and DCS continue to dive after PFO closure and this seems to be fairly safe. Our study suggests a conservative diving profile when there is a residual shunt after PFO closure, to prevent recurrent DCS events.
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| 22. |
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| 23. |
- Escobar Kvitting, John-Peder, et al.
(author)
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Surgical management of outflow tract obstruction after transapical mitral valve implantation
- 2018
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In: Journal of cardiac surgery. - : Wiley-Blackwell Publishing Inc.. - 0886-0440 .- 1540-8191. ; 33:9, s. 545-547
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Journal article (peer-reviewed)abstract
- Left ventricular outflow tract (LVOT) obstruction due to systolic anterior motion of the anterior mitral valve leaflet (AML) is a known complication after mitral valve repair or transfemoral/transapical mitral valve implantation (TMVI). We present a patient with a previous mitral valve repair who developed LVOT obstruction after TMVI in whom the AML was surgically resected using a transaortic approach.
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| 24. |
- Feldt, K., et al.
(author)
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Change in mitral regurgitation severity impacts survival after transcatheter aortic valve replacement
- 2019
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In: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 294, s. 32-36
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Journal article (peer-reviewed)abstract
- Background: The impact of a change in mitral regurgitation (MR) following TAVR is unknown. We studied the impact of baseline MR and early post-procedural change in MR on survival following TAVR. Methods: The SWEDEHEART registry included all TAVRs performed in Sweden. Patients were dichotomized into no/mild and moderate/severe MR groups. Vital status, echocardiographic data at baseline and within 7 days after TAVR were analyzed. Results: 1712 patients were included. 1404 (82%) had no/mild MR and 308 (18%) had moderate/severe MR. Baseline moderate/severe MR conferred a higher mortality rate at 5-year follow-up (adjusted HR 1.29, CI 1.01-1.65, p = 0.04). Using persistent <= mild MR as the reference, when moderate/severe MR persisted or if MR worsened from <= mild at baseline to moderate/severe after TAVR, higher 5-year mortality rates were seen (adjusted HR 1.66, CI 1.17-2.34, p = 0.04; adjusted HR 1.97, CI 1.29-3.00, p = 0.002, respectively). If baseline moderate/severe MR improved to = mild after TAVR no excess mortality was seen (HR 1.09, CI 0.75-1.58, p = 0.67). Paravalvular aortic regurgitation (PVL) was inversely associated with MR improvement after TAVR (OR 0.4, 95%: CI 0.17-0.94; p = 0.034). Atrial fibrillation (OR 2.1, 95% CI: 1.27-3.39, p = 0.004), self-expanding valve (OR 3.8, 95% CI: 2.08-7.14, p < 0.0001), and PVL (4.3, 95% CI 2.32-7.78. p < 0.0001) were associated with MR worsening. Conclusions: Moderate/severe baseline MR in patients undergoing TAVR is associated with a mortality increase during 5 years of follow-up. This risk is offset if MR improves to <= mild, whereas worsening of MR after TAVR is associated with a 2-fold mortality increase.
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| 25. |
- Forsberg, Lena M, et al.
(author)
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Left and right ventricular function in aortic stenosis patients 8 weeks post-transcatheter aortic valve implantation or surgical aortic valve replacement
- 2011
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In: European Journal of Echocardiography. - : Oxford University Press (OUP). - 1525-2167 .- 1532-2114. ; 12:8, s. 603-611
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Journal article (peer-reviewed)abstract
- Aims Knowledge of longitudinal left and right ventricular (LV and RV) function after transcatheter aortic valve implantation (TAVI) is scarce. We hypothesized that the longitudinal systolic biventricular function in aortic stenosis (AS) patients is affected differently by TAVI and surgical aortic valve replacement (SAVR). less thanbrgreater than less thanbrgreater thanMethods and results Thirty-three AS patients (all-TAVI group, age 81 +/- 9 years, 18 female), with EuroSCORE 18 +/- 9%, were accepted for TAVI. Seventeen of these patients were matched (by gender, age, and LV function) to 17 patients undergoing SAVR. Conventional echocardiographic parameters, systolic atrioventricular plane displacement (AVPD) at standard sites and peak systolic velocity (PSV) by pulsed tissue Doppler at basal RV free wall, LV lateral wall, and septum were studied before and 8 weeks after the procedure. Procedural success was 100%, and 30-day mortality 9%. In all TAVI patients, AVPD(lateral), PSV(lateral), AVPD(septal), and PSV(septal) increased (P andlt; 0.001, 0.003, 0.006 and 0.002). When studying the matched patients postoperatively, both the SAVR and TAVI patients had increased PSV(lateral) and AVPD(lateral) (SAVR: P = 0.03 and P = 0.04, TAVI: P = 0.04 and P = 0.01). The PSV(RV) increased in the all-TAVI group (P = 0.007), while the AVPD(RV) was unchanged. SAVR patients had decreased AVPD(RV) (P = 0.001) and PSV(RV) (P = 0.004), while the matched TAVI patients had unchanged RV function parameters. less thanbrgreater than less thanbrgreater thanConclusion An improvement in regional longitudinal LV function in the septal and lateral wall could be seen after TAVI. Among the matched patients, both the TAVI and SAVR patients seemed to improve LV function in the lateral wall. RV systolic function increased in TAVI patients, but was impaired in the matched SAVR group at the 8-week follow-up.
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| 26. |
- Gejl, Kasper Degn, et al.
(author)
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Effects of Acute Exercise and Training on the Sarcoplasmic Reticulum Ca(2+)Release and Uptake Rates in Highly Trained Endurance Athletes
- 2020
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In: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 11
-
Journal article (peer-reviewed)abstract
- Little is presently known about the effects of acute high-intensity exercise or training on release and uptake of Ca(2+)by the sarcoplasmic reticulum (SR). The aims here were to characterize this regulation in highly trained athletes following (1) repeated bouts of high-intensity exercise and (2) a period of endurance training including high-intensity sessions. Eleven cross-country skiers (25 +/- 4 years, 65 +/- 4 mL O-2.kg(-1).min(-1)) performed four self-paced sprint time-trials (STT 1-4) lasting approximate to 4 min each (STT 1-4) and separated by 45 min of recovery; while 19 triathletes and road cyclists (25 +/- 4 years, 65 +/- 5 mL O-2.kg(-1).min(-1)) completed 4 weeks of endurance training in combination with three sessions of high-intensity interval cycling per week. Release (mu mol.g(-1)prot.min(-1)) and uptake [tau (s)] of Ca(2+)by SR vesicles isolated from m.triceps brachiiand m.vastus lateraliswere determined before and after STT 1 and 4 in the skiers and in m.vastus lateralisbefore and after the 4 weeks of training in the endurance athletes. The Ca(2+)release rate was reduced by 17-18% in both limbs already after STT 1 (arms: 2.52 +/- 0.74 to 2.08 +/- 0.60; legs: 2.41 +/- 0.45 to 1.98 +/- 0.51,P< 0.0001) and attenuated further following STT 4 (arms: 2.24 +/- 0.67 to 1.95 +/- 0.45; legs: 2.13 +/- 0.51 to 1.83 +/- 0.36,P< 0.0001). Also, there was a tendency toward an impairment in the SR Ca(2+)uptake from pre STT1 to post STT4 in both arms and legs (arms: from 22.0 +/- 3.7 s to 25.3 +/- 6.0 s; legs: from 22.5 +/- 4.7 s to 25.5 +/- 7.7 s,P= 0.05). Endurance training combined with high-intensity exercise increased the Ca(2+)release rate by 9% (1.76 +/- 0.38 to 1.91 +/- 0.44,P= 0.009), without altering the Ca(2+)uptake (29.6 +/- 7.0 to 29.1 +/- 8.7 s;P= 0.98). In conclusion, the Ca(2+)release and uptake rates by SR in exercising limbs of highly trained athletes declines gradually by repetitive bouts of high-intensity exercise. We also demonstrate, for the first time, that the SR Ca(2+)release rate can be enhanced by a specific program of training in highly trained athletes, which may have important implications for performance parameters.
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| 27. |
- Gejl, Kasper D., et al.
(author)
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Local depletion of glycogen with supra-maximal exercise in human skeletal muscle fibres
- 2017
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In: Journal of Physiology. - 0022-3751 .- 1469-7793. ; 595:9, s. 2809-2821
-
Journal article (peer-reviewed)abstract
- Skeletal muscle glycogen is heterogeneous distributed in three separated compartments (intramyofibrillar, intermyofibrillar and subsarcolemmal). Although only constituting 4-15% of the total glycogen volume, the availability of intramyofibrillar glycogen has been shown to be of particular importance to muscle function. The present study was designed to investigate the depletion of these three sub-cellular glycogen compartments during repeated supra-maximal exercise in elite athletes. Ten elite cross-country skiers (age: 25 +/- 4 yrs., VO2 max : 65 +/- 4 ml kg-1 min-1 , mean +/- SD) performed four approximately 4-minute supra-maximal sprint time trials (STT 1-4) with 45 min recovery. The sub-cellular glycogen volumes in m. triceps brachii were quantified from electron microscopy images before and after both STT 1 and STT 4. During STT 1, the depletion of intramyofibrillar glycogen was higher in type I fibres (-52% [-89:-15%]) than type 2 fibres (-15% [-52:22%]) (P = 0.02), while the depletion of intermyofibrillar glycogen (main effect: -19% [-33:0], P = 0.006) and subsarcolemmal glycogen (main effect: -35% [-66:0%], P = 0.03) was similar between fibre types. In contrast, only intermyofibrillar glycogen volume was significantly reduced during STT 4, in both fibre types (main effect: -31% [-50:-11%], P = 0.002). Furthermore, for each of the sub-cellular compartments, the depletion of glycogen during STT 1 was associated with the volumes of glycogen before STT 1. In conclusion, the depletion of spatially distinct glycogen compartments differs during supra-maximal exercise. Furthermore, the depletion changes with repeated exercise and is fibre type-dependent.
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| 28. |
- Hansson, Nicolaj C., et al.
(author)
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The impact of calcium volume and distribution in aortic root injury related to balloon-expandable transcatheter aortic valve replacement
- 2015
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In: JOURNAL OF CARDIOVASCULAR COMPUTED TOMOGRAPHY. - : ELSEVIER SCIENCE INC. - 1934-5925. ; 9:5, s. 382-392
-
Journal article (peer-reviewed)abstract
- Background: A detailed assessment of calcium within the aortic root may provide important additional information regarding the risk of aortic root injury during transcatheter heart valve replacement (TAVR). Objective: We sought to delineate the effect of calcium volume and distribution on aortic root injury during TAVR. Methods: Thirty-three patients experiencing aortic root injury during TAVR with a balloon-expandable valve were compared with a control group of 153 consecutive TAVR patients without aortic root injury (as assessed by post-TAVR multidetector CT). Using commercial software to analyze contrast-enhanced pre-TAVR CT scans, caltium volume was determined in 3 regions: (1) the overall left ventricular outflow tract (LVOT), extending 10 mm down from the aortic annulus plane; (2) the upper LVOT, extending 2 mm down from the annulus plane; and (3) the aortic valve region. Results: Calcium volumes in the upper LVOT (median, 29 vs 0 mm(3); P less than .0001) and overall LVOT (median, 74 vs 3 mm(3); P = .0001) were higher in patients who experienced aortic root injury compared with the control group. Calcium in the aortic valve region did not differ between groups. Upper LVOT calcium volume was more predictive of aortic root injury than overall LVOT calcium volume (area under receiver operating curve [AUG]; 0.78; 95% confidence interval, 0.69-0.86 vs AUC, 0.71; 95% confidence interval, 0.62-0.82; P = .010). Upper LVOT calcium below the noncoronary cusp was significantly more predictive of aortic root injury compared to calcium underneath the right coronary cusp or the left coronary cusp (AUC, 0.81 vs 0.68 vs 0.64). Prosthesis oversizing greater than20% (likelihood ratio test, P = .028) and redilatation (likelihood ratio test, P = .015) improved prediction of aortic root injury by upper LVOT calcium volume. Conclusion: Calcification of the LVOT, especially in the upper LVOT, located below the noncoronary cusp and extending from the annular region, is predictive of aortic root injury during TAVR with a balloon-expandable valve. (C) 2015 Society of Cardiovascular Computed Tomography. All rights reserved.
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| 29. |
- Hauge, Stale Wagen, et al.
(author)
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Short-term outcome after open-heart surgery for severe chronic rheumatic heart disease in a low-income country, with comparison with an historical control group: an observational study
- 2021
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In: Open heart. - : BMJ PUBLISHING GROUP. - 2053-3624. ; 8:2
-
Journal article (peer-reviewed)abstract
- Objectives Rheumatic heart disease (RHD) is a major burden in low-income and middle-income countries (LMICs). Cardiac surgery is the only curative treatment. Little is known about patients with severe chronic RHD operated in LMICs, and challenges regarding postoperative follow-up are an important issue. At Tikur Anbessa Specialised Hospital, Addis Ababa, Ethiopia, we aimed to evaluate the course and 12-month outcome of patients with severe chronic RHD who received open-heart surgery, as compared with the natural course of controls waiting for surgery and undergoing only medical treatment. Methods Clinical data and outcome measures were registered in 46 patients operated during five missions from March 2016 to November 2019, and compared with the first-year course in a cohort of 49 controls from the same hospitals waiting list for surgery. Adverse events were death or complications such as stroke, other thromboembolic events, bleeding, hospitalisation for heart failure and infectious endocarditis. Results Survival at 12 months was 89% and survival free from complications was 80% in the surgical group. Despite undergoing open-heart surgery, with its inherent risks, outcome measures of the surgical group were non-inferior to the natural course of the control group in the first year after inclusion on the waiting list (p >= 0.45). All except six surgical patients were in New York Heart Association class I after 12 months and 84% had resumed working. Conclusions Cardiac surgery for severe chronic RHD is feasible in LMICs if the service is structured and planned. Rates of survival and survival free from complications were similar to those of controls at 12 months. Functional level and resumption of work were high in the surgical group. Whether the patients who underwent cardiac surgery will have better long-term prognosis, in line with what is known in high-income countries, needs to be evaluated in future studies.
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| 30. |
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| 31. |
- Josefsson, Ann, et al.
(author)
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Reproductive patterns and pregnancy outcomes in women with congenital heart disease - a Swedish population-based study
- 2011
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In: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 90:6, s. 659-665
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Journal article (peer-reviewed)abstract
- Objective. To study women diagnosed with congenital heart disease (CHD) with respect to characteristics related to their own births, their subsequent likelihood of giving birth and the obstetric and neonatal outcomes of their pregnancies. Design. Population-based register study. Population. All women born in 1973-1983 who were alive and living in Sweden at 13 years of age (n=500 245). Methods. Women diagnosed with CHD (n=2 216) were compared with women without CHD (n=492 476). A total of 188 867 mother-firstborn-offspring pairs were identified and available for analysis. Results. Mothers of women with CHD were more often older and single/unmarried. Women with CHD were more often born preterm or small-for-gestational age (SGA) than women without CHD, more likely to have been born with a cesarean section, to have given birth during the study period, and to be younger at the time of their first pregnancy. Women with CHD were also more prone to give birth to children preterm or SGA and their babies were more often delivered by cesarean section with a higher frequency of congenital abnormality. Conclusions. Women with CHD were more likely to have been born preterm or SGA and these outcomes were repeated in the next generation. Women with CHD should not be discouraged from pregnancy. Prenatal diagnostics should be discussed and offered to these women, as there is an increased risk for congenital abnormalities.
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| 32. |
- Kanoni, Stavroula, et al.
(author)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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In: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
-
Journal article (peer-reviewed)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 33. |
- Kernell, Kristina, et al.
(author)
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Congenital heart disease in men - birth characteristics and reproduction : a national cohort study.
- 2014
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In: BMC Pregnancy and Childbirth. - : BioMed Central (BMC). - 1471-2393. ; 14, s. 187-
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Journal article (peer-reviewed)abstract
- BACKGROUND: Women with congenital heart disease (CHD) are more often born preterm or small-for-gestational age and with a caesarean section. This pattern together with an increased risk of congenital anomalies seems to be repeated in the next generation. Information on the effect of paternal CHD on their offspring is sparse. In this study we investigated if men with CHD differ from those who do not have CHD with respect to characteristics related to their own births, their reproductive patterns and the neonatal outcomes of their children.METHODS: In this national cohort study data were derived from Swedish population-based registries. The population consists of all men born in 1973-1983 who were alive and living in Sweden at 13 years of age (n = 522 216). The index group is men with CHD (n = 2689). Men diagnosed with CHD were compared with men without CHD. The CHD were also divided into two groups, complex and simple CHD and comparisons between the groups were made.RESULTS: Men with CHD are more likely to have been born preterm (p < 0.001), small-for gestational-age (p < 0.001) or large-for-gestational-age (p < 0.001) than men without CHD. They are also more likely to have been the result of a twin pregnancy (p < 0.001) and to have been delivered by caesarean section (p < 0.001). Men with CHD have a decreased likelihood to become fathers compared to non-CHD men and in this study their offspring do not have a higher incidence of CHD than offspring to non-CHD fathers. The neonatal outcomes of children of men with CHD do not differ from the outcomes of children of non-CHD men.CONCLUSIONS: Men with CHD were more often born with non-optimal characteristics compared to men without the condition. However, the increased risk does not repeat itself in the next generation. This knowledge can lead to improved preconception counselling for couples in which the father has a CHD.
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| 34. |
- Krynska, Aleksandra, et al.
(author)
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Three-dimensional echocardiography to identify right ventricular dilatation in patients with corrected Fallot anomaly or pulmonary stenosis
- 2021
-
In: Clinical Physiology and Functional Imaging. - : Wiley-Blackwell Publishing Inc.. - 1475-0961 .- 1475-097X. ; 41:1, s. 51-61
-
Journal article (peer-reviewed)abstract
- Background 3-Dimensional Echocardiography allows measuring volumes and parameters of myocardial deformation (strain). Myocardial strain has been suggested to be superior to conventional echo parameters in the assessment of right ventricular (RV) function. Myocardial strain can be assessed by cardiac magnetic resonance (CMR) or two- and three-dimensional echocardiography (2D and 3DEcho). We performed a comprehensive assessment of the RV based on 3DEcho and compared the results with those based on CMR and 2DEcho. Methods 36 patients with corrected heart defects underwent CMR and 3DEcho to assess RV volume, strain and cardio pulmonary exercise testing with peak VO2 measurement. 2DEcho was used for reference. Results There was a moderate correlation between 3DEcho and CMR for measuring RV end-diastolic and end-systolic volumes (r = .82 and .72). 3DEcho tended to underestimate the RV volumes, mean difference EDV 8.5 +/- 33 ml (CI -2.8; 19.7 ml) and ESV 13.2 +/- 29 ml (CI 3.3; 23 ml). According to method-specific reference values for RVEDV, 34/35 (3DEcho) and 29/36 (CMR) were dilated. Among those dilated according to CMR, all were identified by 3DEcho. The coefficient of correlation between RV atrioventricular plane displacement measured by CMR and tricuspid annular plane systolic excursion measured by 3D and 2DEcho was r = .6 for both. 2DEcho measured lower LV volumes than CMR. LVEF and GLS were similar in 2DEcho, 3DEcho and CMR. Patients with CMR-determined RV free wall strain <= -14% tended to have lower peak VO2. Conclusions Although 3DEcho underestimated RV volumes, it successfully identified all patients with RV dilatation based on method-specific reference values.
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| 35. |
- Kühme, Tobias, 1963-, et al.
(author)
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Rupture of a synthetic VSD patch 28 years after total correction of Fallot's anomaly
- 2006
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In: Annals of Thoracic Surgery. - : Elsevier BV. - 0003-4975 .- 1552-6259. ; 81:4, s. 1510-1512
-
Journal article (peer-reviewed)abstract
- Patients operated on for complex congenital heart malformations need continuous follow-up. We present a male patient born in 1948 with Fallot's anomaly. A total correction was performed when he was 21 years old. Twenty-eight years after the operation, at routine follow-up, he presented with a significant left-to-right shunt because of a new ventricular septal defect. During the operation we found the original patch to be fractured with a central perforation. The patient received a new patch and has been without any clinical symptoms since. © 2006 by The Society of Thoracic Surgeons.
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| 36. |
- Mahajan, Anubha, et al.
(author)
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Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes
- 2018
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In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:4, s. 559-571
-
Journal article (peer-reviewed)abstract
- We aggregated coding variant data for 81,412 type 2 diabetes cases and 370,832 controls of diverse ancestry, identifying 40 coding variant association signals (P < 2.2 × 10−7); of these, 16 map outside known risk-associated loci. We make two important observations. First, only five of these signals are driven by low-frequency variants: even for these, effect sizes are modest (odds ratio ≤1.29). Second, when we used large-scale genome-wide association data to fine-map the associated variants in their regional context, accounting for the global enrichment of complex trait associations in coding sequence, compelling evidence for coding variant causality was obtained for only 16 signals. At 13 others, the associated coding variants clearly represent ‘false leads’ with potential to generate erroneous mechanistic inference. Coding variant associations offer a direct route to biological insight for complex diseases and identification of validated therapeutic targets; however, appropriate mechanistic inference requires careful specification of their causal contribution to disease predisposition.
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| 37. |
- Marouli, Eirini, et al.
(author)
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Rare and low-frequency coding variants alter human adult height
- 2017
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
-
Journal article (peer-reviewed)abstract
- Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
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| 38. |
- Nielsen, Niels Erik
(author)
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Clinical and Laboratory Investigations in Postmenopusal Women with Unstable Coronary Artery Disease
- 2000
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Doctoral thesis (other academic/artistic)abstract
- Coronary artery disease (CAD) is the major cause of death in both sexes in the western world. In men with chest pain the diagnostic methods are more useful than in women. An exercise test is considered less reliable in women, mostly due to a high percentage offalse positive tests. Furthermore, 20-40% of women with typical angina have normal vessels at coronary angiography. The mechanisms behind the chest pain in these patients are unknown, but could be due to disturbances in endothelial, thrombogenetic and/or fibrinolytic function.In a prospective multicentre trial we examined 200 postmenopausal women with unstable CAD and 101 healthy controls. At coronary angiography 15% had normal vessels, 14% had non-significant atherosclerosis and 71% had at least one significant stenosis.The diagnostic information from basic clinical parameters, ECG and an early exercise test were evaluated. The prevalence of coronary atherosclerosis was high, 85%, and the early exercise test was just as valuable as in men for identifying patients with significant CAD.Endothelial markers, cyclic GMP (cGMP) and immunoreactive endothelin (irET), were analysed regarding presence or not of coronary atherosclerosis. Patients with normal vessels had low levels of ir-Ef, indicating different mechanisms for ischemia/angina in these patients compared with patients with atherosclerosis. No differences were found regarding cGMP, unless the patient had long-term nitroglycerin treatment, which increased plasma cGMP. Patients with exerciseinduced ischemia had higher cGMP plasma levels compared to those without. This may reflect a general compensatory mechanism.New lipid variables, apolipoproteins and lipoprotein particles, were no better than the routine lipid examination in separating women with and without coronary atherosclerosis, and the measurement of apolipoproteins and lipoprotein particles on the basis of diagnostic accuracy alone is not justified. Also, elevated triglycerides was most pronounced in women with unstable CAD and coronary atherosclerosis.Plasma total homocysteine (tHey) is considered a risk factor for CAD, but the relationship between tHey and well-defined CAD in women is still unclear. Mild hyperhomocysteinemia was not related to the risk of unstable CAD in postmenopausal women. Our study stresses the importance of adjusting tHey for the covariates, i.e. age and serum values of folate, vitamin Bl2 and creatinine.Fibrinolytic and coagulation variables did neither reveal signs of disturbed fibrinolysis nor were in favour of a hypercoagulable/hyperthrombotic state in patients with unstable CAD and normal vessels.In summary, the prevalence of coronary atherosclerosis in postmenopausal women with signs and symptoms of unstable CAD is high. An early exercise test together with basic clinical parameters is a valuable diagnostic tool. Although there were differences in biochemical markers between patients with and without coronary atherosclerosis, the overlapping between the groups was high. No clinically useful test to separate these two groups was found. Patients with normal vessels were much alike the control group and it is still unclear whether these patients have CAD without atherosclerosis or another mechanism for their chest pain.
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| 39. |
- Nielsen, Niels Erik, et al.
(author)
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Fibrinolytic Variables in Postmenopausal Women with Unstable Coronary Artery Disease
- 2001
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In: Journal of Thrombosis and Thrombolysis. - 0929-5305 .- 1573-742X. ; 12:3, s. 217-223
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Journal article (peer-reviewed)abstract
- Objectives: Many women with typical anginal chest pain have normal coronary angiograms. The pathogenetic mechanisms behind the chest pain in these patients is unknown but may be due to altered fibrinolytic function enhancing thrombosis formation. We evaluated the two key components of the fibrinolytic system, tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) in women with clinical signs of unstable coronary artery disease (CAD).Methods and results: 158 patients with unstable CAD and 101 controls were examined. Of the patients 16% had normal vessels and 84% coronary atherosclerosis at coronary angiography. Mean plasma concentration of t-PA-ag, but not of PAI-1-act was higher in patients than in controls (t-PA-ag: 2.12 (2.05;2.19) vs. 1.98 (1.89;2.07), p<0.05; PAI-1-act: 1.55 (1.35;1.74) vs. 1.49 (1.24;1.73), p¼n.s.). Patients with coronary atherosclerosis had significantly higher mean plasma levels of both t-PA-ag and PAI-1-act than patients with normal coronary vessels (t-PA-ag: 2.16 (2.08;2.33) vs. 1.94 (1.78;2.10), p<0.05; PAI-1-act: 1.68 (1.47;1.90) vs. 0.82 (0.43;1.21), p<0.01), and these differences were seen whether markers of myocardial damage were elevated or not. Mean plasma levels of PAI-1-act in patients with normal coronary vessels were even lower than in the control group (p<0.05). Almost all significant differences in mean plasma t-PA-ag and PAI-1-act disappeared after adjustments for known covariates.Conclusion: Our results indicate, regardless of myocardial marker elevation or not, an activated fibrinolytic system in postmenopausal women with unstable CAD and coronary atherosclerosis, but not in the same group of patients with normal coronary vessels. This argues against reduced fibrinolytic capacity in the latter patients and therefore against thrombosis formation as the cause of chest pain in these women. However, we cannot exclude that the differences can be an effect of inequality among some common risk factors between the groups.
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| 40. |
- Nielsen, Niels Erik, et al.
(author)
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Markers of hypercoagulation and von Willebrand factor in postmenopausal women with unstable coronary artery disease. Discriminatory ability regarding unstable coronary artery disease and coronary atherosclerosis using receiver operating characteristics
- 2000
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In: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 248:2, s. 151-158
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Journal article (peer-reviewed)abstract
- Objectives. Many women with typical anginal chest pain have normal coronary angiograms. The pathogenetic mechanisms behind the chest pain in these patients are unknown but may be due to increased thrombogenicity. We evaluated markers of hypercoagulation and thrombosis in women with clinical signs of unstable coronary artery disease (CAD).Methods and results. A total of 158 patients with unstable CAD and 101 controls were examined: 16% of the patients had normal vessels and 84% had coronary atherosclerosis at coronary angiography. Mean plasma concentrations of von Willebrand factor antigen, soluble fibrin (SF), thrombin–antithrombin complex and d-dimer were significantly higher, whereas there was no difference regarding prothrombin fragment 1+2 between patients and controls. Patients with coronary atherosclerosis had higher mean plasma levels for most variables compared with those with normal coronary vessels, although only significantly higher for SF. d-Dimer was significantly higher in patients with normal coronary vessels compared with the control group. Although multivariate analyses showed strong significant correlations of the haemostatic variables to the diagnosis of unstable CAD, receiver operating characteristics (ROC) revealed that none of the variables represented high diagnostic accuracy in separating patients with unstable CAD. Likewise, none of the variables was particularly good at identifying coronary atherosclerosis.Conclusion. Our results are in favour of a hypercoagulable state in postmenopausal women with unstable CAD and coronary atherosclerosis, whereas this does not seem to be the case in patients with normal vessels. ROC revealed no variable to be particularly clinically useful in separating patients from controls or patients from those without coronary atherosclerosis.
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| 41. |
- Nielsen, Niels Erik, et al.
(author)
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Markers of hypercoagulation, von Willebrand factor and anticardiolipin antibodies in postmenopausal women with unstable coronary artery disease : Discriminatory Ability Regarding Unstable Coronary Artery Disease and Coronary Atherosclerosis Using Receiver Operating Characterstics
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Other publication (other academic/artistic)abstract
- Aims - Many women with typical anginal chest pain have normal coronary angiograms. The pathogenetic mechanisms behind the chest pain in these patients are unknown but may be due to increased thrombogenecity. We evaluated markers of hypercoagulation and thrombosis in women with clinical signs of unstable coronary artery disease (CAD).Methods and results - 158 patients with unstable CAD and 101 controls were examined. 16% of the patients had nonnal vessels and 84% had coronary atherosclerosis at coronary angiography. Mean plasma concentrations of von Willebrand factor-antigen, soluble fibrin (SF), thrombin-antithrombin complex and Ddimer were significantly higher, whereas there was no difference regarding prothrombin fragment 1 +2 between patients and controls. Patients with coronary atherosclerosis had higher mean plasma levels for most variables compared to those with normal coronary vessels, but the only significant difference was for SF. D-dimer was significantly higher in patients with nonnal coronary vessels compared to the control group. Anticardiolipin antibody (ACA) levels were significantly lower in the patient group compared to the control group. Receiver operating characteristics (ROC) showed that none of the variables represented high diagnostic accuracy in distinguishing patients with unstable CAD from healthy controls, or patients with from those without coronary atherosclerosis.Conclusion - Our results are in favour of a hypercoagulable state in postmenopausal women with unstable CAD and coronary atherosclerosis, even in the absence of myocardial marker elevation, whereas this does not seem to be the case in patients with nonnal vessels. ROC revealed no variable to be particularly clinical useful in separating patients and control or patients with and without coronary atherosclerosis.
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| 42. |
- Nielsen, Niels Erik, et al.
(author)
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Minimizing the risk for left ventricular rupture during transcatheter aortic valve implantation by reducing the presence of stiff guidewires in the ventricle
- 2019
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In: Interactive Cardiovascular and Thoracic Surgery. - : OXFORD UNIV PRESS. - 1569-9293 .- 1569-9285. ; 29:3, s. 365-370
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Journal article (peer-reviewed)abstract
- OBJECTIVES: The presence of a stiff guidewire in the apex of the left ventricle (LV) is a known risk factor for LV perforation. Our goal was to minimize the risk of LV rupture during transcatheter aortic valve implantation (TAVI) by omitting the interaction between the stiff guidewire and the LV apex using a modified procedure. METHODS: A TAVI protocol designed to allow minimal interaction between a stiff guidewire and the LV was developed in Linkoping University Hospital in Sweden. A total of 316 patients were treated exclusively by this approach between March 2014 and May 2018. RESULTS: All procedures were completed successfully. There were no cases (0%) of ventricular perforation. Only 1 patient (0.3%) had a pericardial effusion, and it was due to annulus rupture. There was 1 case of acute kidney injury (0.3%). Five patients (1.6%) required a new permanent pacemaker. Stroke occurred in 3 patients (0.9%). No patient had valve embolization. Vascular complications were experienced by 6 patients (1.9%). A mild paravalvular leak occurred in 27 (8.5%) patients. At 30 days post-TAVI, 6 patients (2%) had died. The mortality rate at 1 year was 8.6% (n = 20/232). CONCLUSIONS: Our series shows that TAVI without the prolonged use of a stiff guidewire in the LV apex is feasible. The risk of LV perforation is eliminated by this approach, and other procedural complications are limited.
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| 43. |
- Nielsen, Niels Erik, et al.
(author)
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Plasma levels of cyclic GMP and endothelin in postmenopausal women with unstable coronary artery disease
- 1999
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In: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa UK Limited. - 0036-5513 .- 1502-7686. ; 59:5, s. 325-334
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Journal article (peer-reviewed)abstract
- Many women with typical anginal chest pain have normal coronary angiograms, which may be due to altered endothelial function. We evaluated the endothelial markers cyclic GMP (cGMP) and immunoreactive endothelin (ir-ET) regarding presence of coronary atherosclerosis in women with clinical signs of unstable coronary artery disease (CAD). Plasma levels of cGMP and ir-ET were determined in 118 patients and 84 controls. Ischaemia was evaluated at an exercise test. Of the patients 20% had normal vessels, 14% insignificant CAD and 66% significant stenosis at coronary angiography. Mean (95% CI) concentration of cGMP (nmol/l) was higher in patients than in controls (5.05 (4.53; 5.58) vs. 3.79 (3.34; 4.23)). Separating patients according to daily intake of nitroglycerin, only patients with this medication had significantly higher cGMP level (5.73 (4.88; 6.58)), whereas the difference between those without (4.35 (3.76; 4.94)) and controls disappeared. Patients with ischaemia at exercise test had higher cGMP level than those without (6.01 (5.13; 6.88) vs. 4.30 (3.66; 4.94)), even after adjusting for nitroglycerin treatment. ir-ET (pmol/l) was lower in patients with normal vessels than patients with coronary atherosclerosis (0.83 (0.78; 0.88) vs. 0.98 (0.92; 1.04)) and than the control group (0.91 (0.87; 0.94)). The difference between the control group and patients with atherosclerosis was also significant. Patients with unstable CAD and long-term nitroglycerin treatment have increased cGMP level. Patients with exercise-induced ischaemia have higher cGMP level than those without, irrespective of nitroglycerin treatment, which may reflect a general compensatory mechanism. Patients with normal vessels have low level of ir-ET, indicating different mechanisms for ischaemia/angina in these patients compared with patients with atherosclerosis.
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| 44. |
- Nielsen, Niels Erik, et al.
(author)
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Plasma lipoprotein particle concentrations in postmenopausal women with unstable coronary artery disease : Analysis of diagnostic accuracy using receiver operating characteristics
- 2000
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In: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 247:1, s. 43-52
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Journal article (peer-reviewed)abstract
- Background.The contribution of plasma lipids to cardiovascular risk is usually evaluated by measuring plasma concentrations of total cholesterol, triglycerides and HDL cholesterol, and calculating LDL cholesterol concentration. We investigated plasma concentrations of apolipoproteins and lipoprotein particles in women with unstable coronary artery disease (CAD) to evaluate whether these, better than the routine lipid status, could differentiate women with and without coronary atherosclerosis.Methods. Blood samples for lipid analyses were collected from 119 angiographically examined postmenopausal 49–79-year-old women with unstable CAD, and from 101 age-matched controls. Mean plasma concentrations were compared and the discriminatory ability of the different variables were tested using receiver operating characteristics (ROC).Results. At coronary angiography 19% had normal vessels and 81% had coronary atherosclerosis. A disturbed triglyceride metabolism was the most pronounced lipid abnormality in women with unstable CAD and coronary atherosclerosis. ROC showed that none of the evaluated variables had a particularly high discriminatory power regarding unstable CAD or coronary atherosclerosis. The ratio cholesterol/HDL cholesterol was best with an ROC area of 0.79. Furthermore, the newer lipid variables, i.e. lipoprotein particles and apolipoproteins, were no better than the traditional variables.Conclusion. Lipoprotein changes reflecting a disturbed triglyceride metabolism are most pronounced in women with unstable CAD and coronary atherosclerosis. Lipoprotein particles and apolipoproteins alone were no better than lipids and lipoproteins in separating women with from those without coronary atherosclerosis. Our study does not support the measurement of apolipoproteins and lipoprotein particles on the basis of diagnostic accuracy alone.
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| 45. |
- Nielsen, Niels Erik, et al.
(author)
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Plasma total homocysteine levels in postmenopausal women with unstable coronary artery disease
- 2000
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In: Atherosclerosis. - 0021-9150 .- 1879-1484. ; 151:2, s. 423-431
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Journal article (peer-reviewed)abstract
- An elevated plasma total homocysteine (tHcy) level is considered a risk factor for coronary artery disease (CAD), but the relationship between plasma tHcy and well-defined CAD in women is still unclear. Plasma tHcy concentrations and the covariates serum folate, vitamin B12, and creatinine were analysed in 157 angiographically examined postmenopausal women with unstable CAD and in 101 healthy controls. At coronary angiography, 16% had normal vessels and 84% had coronary atherosclerosis. Mean plasma tHcy concentration (μmol/l, 95% confidence interval) did not differ in patients compared to controls (13.1 (12.3–13.8) vs. 12.5 (11.6–13.5)) or in patients with or without coronary atherosclerosis (13.3 (12.4–14.1) vs. 12.0 (10.8–13.2)). A trend to an increasing plasma tHcy with increasing degree of coronary atherosclerosis was attenuated after adjustment for age and the previous mentioned covariates. Odds ratio for the risk of coronary artery disease and coronary atherosclerosis in hyperhomocysteinemic patients (≥90th percentile in controls) was approximately 3. However, the confidence interval included unity in half of the groups and the significance was therefore difficult to judge. Receiver operating characteristics showed age to be the only variable with a significant discriminatory ability regarding the presence of coronary atherosclerosis (area 0.77). Mild hyperhomocysteinemia seems not to be related to the risk of unstable CAD in postmenopausal women. The trend towards higher plasma tHcy with increasing degree of coronary atherosclerosis may be a marker of the disease. In future studies adjustment for age and the other three covariates should be considered.
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| 46. |
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| 47. |
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| 48. |
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| 49. |
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| 50. |
- Nielsen, Niels Erik, et al.
(author)
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Transvenous Implantation of a Stent Valve for Calcified Native Mitral Stenosis
- 2015
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In: Annals of Thoracic Surgery. - : ELSEVIER SCIENCE INC. - 0003-4975 .- 1552-6259. ; 100:1, s. E21-E23
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Journal article (peer-reviewed)abstract
- We used a modified combination of the transseptal and transapical methods to facilitate the controlled delivery and use of a stent valve in a patient with calcified native mitral stenosis. A loop from the right femoral vein passing transseptally and then through the apex of the left ventricle was created, enabling highly controlled positioning and deployment of the stent valve.
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