John-Peder Kvitting

• Ravnestad, Håvard; Ahmed, Salaheldin; Østby, Carol Margaret; Gude, Einar; Kvitting, John-Peder & Broch, Kaspar [Show all 10 contributors for this article] (2026). The association between soluble ST2 and transplant-free survival in precapillary pulmonary hypertension. JHLT Open. 14. doi: 10.1016/j.jhlto.2026.100661. Full text in Research Archive
• Holt, Margrethe Flesvig; Michelsen, Annika Elisabet; Flø, August Magnus Stensrød; Khan, Yusuf; Bjørnø, Vilde & Skjelland, Mona [Show all 17 contributors for this article] (2025). Hepatocyte Growth Factor: A Marker of Cardiac Function, Mortality, and Disease Subtype in Cardiac Amyloidosis. JACC: Advances. 4(6). doi: 10.1016/j.jacadv.2025.101828. Full text in Research Archive
• Ribic, Darijan; Remme, Espen; Smiseth, Otto Armin; Massey, Richard; Eek, Christian & Kvitting, John-Peder [Show all 9 contributors for this article] (2024). Non-invasive myocardial work in aortic stenosis: Validation and improvement in left ventricular pressure estimation. European Heart Journal-Cardiovascular Imaging. ISSN 2047-2404. 25(2), p. 201–212. doi: 10.1093/ehjci/jead227. Full text in Research Archive Show summary

  Aims The non-invasive myocardial work index (MWI) has been validated in patients without aortic stenosis (AS). A thorough assessment of methodological limitations is warranted before this index can be applied to patients with AS. Methods and results We simultaneously measured left ventricular pressure (LVP) by using a micromanometer-tipped catheter and obtained echocardiograms in 20 patients with severe AS. We estimated LVP curves and calculated pressure–strain loops using three different models: (i) the model validated in patients without AS; (ii) the same model, but with pressure at the aortic valve opening (AVO) adjusted to diastolic cuff pressure; and (iii) a new model based on the invasive measurements from patients with AS. Valvular events were determined by echocardiography. Peak LVP was estimated as the sum of the mean aortic transvalvular gradient and systolic cuff pressure. In same-beat comparisons between invasive and estimated LVP curves, Model 1 significantly overestimated early systolic pressure by 61 ± 5 mmHg at AVO compared with Models 2 and 3. However, the average correlation coefficients between estimated and invasive LVP traces were excellent for all models, and the overestimation had limited influence on MWI, with excellent correlation (r = 0.98, P < 0.001) and good agreement between the MWI calculated with estimated (all models) and invasive LVP. Conclusion This study confirms the validity of the non-invasive MWI in patients with AS. The accuracy of estimated LVP curves improved when matching AVO to the diastolic pressure in the original model, mirroring that of the AS-specific model. This may sequentially enhance the accuracy of regional MWI assessment.

• Persson, Robert Matongo; Aguilera, Hans Martin Dahl; Grong, Ketil; Kvitting, John-Peder Escobar; Stangeland, Lodve & Haaverstad, Rune [Show all 8 contributors for this article] (2024). Characterisation of global and regional mitral annular strains in an acute porcine model. Interdisciplinary CardioVascular and Thoracic Surgery. 39(3). doi: 10.1093/icvts/ivae154. Full text in Research Archive Show summary

  OBJECTIVES: This study aimed to explore regional mitral annular strain using a novel computational method. METHODS: Eight pigs underwent implantation with piezoelectric transducers around the mitral annulus. Interventions of pre- and afterload were performed by inferior vena cava constriction and endovascular balloon occlusion of the descending aorta. The mitral annulus was reconstructed in a mathematical model and divided into 6 segments. Global and segmental annular strain were calculated from a discrete mathematical representation. RESULTS: Global annular strain gradually decreased after isovolumetric contraction until late systole. Mitral annular end-systolic strain demonstrated shortening in all segments except the anterior segment, which showed the least deformation. The P2 annular segment demonstrated the most end-systolic shortening (–7.6 ± 1.1% at baseline, P < 0.001 compared to anterior segment). Systolic global annular strain showed no significant change in response to load interventions but correlated positively with left ventricular contractility at baseline and after preload reduction. CONCLUSIONS: Mitral annular systolic strain demonstrates cyclical variations with considerable regional heterogeneity, with the most pronounced deformation in posterior annular segments. Measurements appear independent of changes to pre- and afterload.

• Zabirnyk, Arsenii; Evensen, Daria; Kvitting, John-Peder; Kaljusto, Mari-Liis; Stensløkken, Kåre-Olav & Vaage, Ingvar Jarle (2024). Hyperglycemia-simulating environment attenuated experimentally induced calcification in cultured human aortic valve interstitial cells. Scandinavian Cardiovascular Journal. ISSN 1401-7431. 58(1). doi: 10.1080/14017431.2024.2353070. Full text in Research Archive Show summary

  Objectives: The role of diabetes mellitus as a risk factor for the development of calcific aortic valve disease has not been fully clarified. Aortic valve interstitial cells (VICs) have been suggested to be crucial for calcification of the valve. Induced calcification in cultured VICs is a good in vitro model for aortic valve calcification. The purpose of this study was to investigate whether increased glucose levels increase experimentally induced calcification in cultured human VICs. Design: VICs were isolated from explanted calcified aortic valves after valve replacement. Osteogenic medium induced calcification of cultured VICs at different glucose levels (5, 15, and 25 mM). Calcium deposits were visualized using Alizarin Red staining and measured spectrophotometrically. Results: The higher the glucose concentration, the lower the level of calcification. High glucose (25 mM) reduced calcification by 52% compared with calcification at a physiological (5 mM) glucose concentration (correlation and regression analysis: r = −0.55, p = .025 with increased concentration of glucose). Conclusions: In vitro hyperglycemia-like conditions attenuated calcification in VICs. High glucose levels may trigger a series of events that secondarily stimulate calcification of VICs in vivo.

• Ravnestad, Håvard; Murbræch, Klaus; Gjønnæss, Eyvind; Andersen, Rune; Moe, Natasha & Birkeland, Sigurd [Show all 13 contributors for this article] (2024). Right ventricular remodelling and long-term survival after pulmonary endarterectomy versus balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension. Heart. ISSN 1355-6037. doi: 10.1136/heartjnl-2024-324243. Full text in Research Archive
• Törnudd, Mattias; Ramström, Sofia; Kvitting, John-Peder; Alfredsson, Joakim; Nyberg, Linnea & Björkman, Erik [Show all 7 contributors for this article] (2023). Platelet Function is Preserved After Moderate Cardiopulmonary Bypass Times But Transiently Impaired After Protamine. Journal of Cardiothoracic and Vascular Anesthesia. ISSN 1053-0770. 37(7), p. 1110–1120. doi: 10.1053/j.jvca.2023.03.013. Full text in Research Archive Show summary

  Objectives Previous studies have described impaired platelet function after cardiopulmonary bypass (CPB). Whether this is still valid in contemporary cardiac surgery is unclear. This study aimed to quantify changes in function and number of platelets during CPB in a present-day cardiac surgery cohort. Design Prospective, controlled clinical study. Setting A single-center university hospital. Participants Thirty-nine patients scheduled for coronary artery bypass graft surgery with CPB. Interventions Platelet function and numbers were measured at 6 timepoints in 39 patients during and after coronary artery bypass graft surgery; at baseline before anesthesia, at the end of CPB, after protamine administration, at intensive care unit (ICU) arrival, 3 hours after ICU arrival, and on the morning after surgery. Measurements and Main Results Platelet function was assessed with impedance aggregometry and flow cytometry. Platelet numbers are expressed as actual concentration and as numbers corrected for dilution using hemoglobin as a reference marker. There was no consistent impairment of platelet function during CPB with either impedance aggregometry or flow cytometry. After protamine administration, a decrease in platelet function was seen with impedance aggregometry and for some markers of activation with flow cytometry. Platelet function was restored 3 hours after arrival in the ICU. During CPB (85.0 ± 21 min), the number of circulating platelets corrected for dilution increased from 1.73 ± 0.42 × 109/g to 1.91 ± 0.51 × 109/g (p < 0.001). Conclusions During cardiac surgery with moderate CPB times, platelet function was not impaired, and no consumption of circulating platelets could be detected. Administration of protamine transiently affected platelet function.

• Ravnestad, Håvard; Andersen, Rune; Birkeland, Sigurd; Svalebjørg, Morten; Lingaas, Per Snorre & Gude, Einar [Show all 10 contributors for this article] (2023). Pulmonary endarterectomy and balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension: Comparison of changes in hemodynamics and functional capacity. Pulmonary Circulation (PC). ISSN 2045-8932. 13(1), p. 1–12. doi: 10.1002/pul2.12199. Full text in Research Archive Show summary

  Abstract The treatment of choice for chronic thromboembolic pulmonary hypertension (CTEPH) is pulmonary endarterectomy (PEA). Balloon pulmonary angioplasty (BPA) is an emerging option for inoperable patients. Comparisons of the hemodynamic and functional outcome between these treatments are scarce. In this single‐center observational cohort study, we compared hemodynamics by right heart catheterization and peak oxygen consumption before and 5 months (±14 days) after either PEA or BPA. Comprehensive evaluation and selection for PEA or BPA was performed by an expert CTEPH team. Fourty‐two and fourty consecutive patients were treated with PEA or BPA, respectively. Demographics were similar between groups. Both PEA and BPA significantly reduced mean pulmonary artery pressure (from 46 ± 11 mmHg at baseline to 28 ± 13 mmHg at follow‐up; p  &lt; 0.001 and from 43 ± 12 mmHg to 31 ± 9 mmHg; p  &lt; 0.001) and pulmonary vascular resistance (from 686 ± 347 dyn s cm −5 at baseline to 281 ± 197 dyn s cm −5 at follow‐up; p  &lt; 0.001 and from 544 ± 322 dyn s cm −5 to 338 ± 180 dyn s cm −5 ; p  &lt; 0.001), with significantly lower reductions for both parameters in the former group. However, cardiopulmonary exercise testing revealed no significant between group differences in exercise capacity. Diffusion capacity for carbon monoxide at baseline was the only follow‐up predictor for peak VO 2 . In our study, PEA reduced pulmonary pressures more than BPA did, but similar improvements were observed for exercise capacity. Thus, while long term data after BPA is lacking, BPA treated CTEPH patients can expect physical gains in line with PEA.

• Persson, Robert; Aguilera, Hans Martin Dahl; Kvitting, John-Peder; Grong, Ketil; Prot, Victorien Emile & Salminen, Pirjo-Riitta [Show all 11 contributors for this article] (2023). Mitral annular dynamics are influenced by left ventricular load and contractility in an acute animal model. Physiological Reports. 11(7). doi: 10.14814/phy2.15665. Full text in Research Archive Show summary

  The purpose of this study was to investigate the effects of loading conditions and left ventricular (LV) contractility on mitral annular dynamics. In 10 anesthetized pigs, eight piezoelectric transducers were implanted equidistantly around the mitral annulus. High-fidelity catheters measured left ventricular pressures and the slope of the end-systolic pressure-volume relationship (Ees) determined LV contractility. Adjustments of pre- and afterload were done by constriction of the inferior caval vein and occlusion of the descending aorta. Mitral annulus area indexed to body surface area (MAAi), annular circularity index (ACI), and non-planarity angle (NPA) were calculated by computational analysis. MAAi was more dynamic in response to loading interventions than ACI and NPA. However, MAAi maximal cyclical reduction (−Δr) and average deformational velocity (− ) did not change accordingly (p = 0.31 and p = 0.22). Reduced Ees was associated to attenuation in MAAi-Δr and MAAi- (r2 = 0.744; p = 0.001 and r2 = 0.467; p = 0.029). In conclusion, increased cardiac load and reduced LV contractility may cause deterioration of mitral annular dynamics, likely impairing coaptation and increasing susceptibility to valvular incompetence.

• Semenova, Daria; Zabirnyk, Arsenii; Lobov, Arseniy; Boyarskaya, Nadezda; Kachanova, Olga & Uspensky, Vladimir [Show all 16 contributors for this article] (2022). Multi-omics of in vitro aortic valve calcification. Frontiers in Cardiovascular Medicine. 9. doi: 10.3389/fcvm.2022.1043165. Full text in Research Archive Show summary

  Heart valve calcification is an active cellular and molecular process that partly remains unknown. Osteogenic differentiation of valve interstitial cells (VIC) is a central mechanism in calcific aortic valve disease (CAVD). Studying mechanisms in CAVD progression is clearly needed. In this study, we compared molecular mechanisms of osteogenic differentiation of human VIC isolated from healthy donors or patients with CAVD by RNA-seq transcriptomics in early timepoint (48 h) and by shotgun proteomics at later timepoint (10th day). Bioinformatic analysis revealed genes and pathways involved in the regulation of VIC osteogenic differentiation. We found a high amount of stage-specific differentially expressed genes and good accordance between transcriptomic and proteomic data. Functional annotation of differentially expressed proteins revealed that osteogenic differentiation of VIC involved many signaling cascades such as: PI3K-Akt, MAPK, Ras, TNF signaling pathways. Wnt, FoxO, and HIF-1 signaling pathways were modulated only at the early timepoint and thus probably involved in the commitment of VIC to osteogenic differentiation. We also observed a significant shift of some metabolic pathways in the early stage of VIC osteogenic differentiation. Lentiviral overexpression of one of the most upregulated genes (ZBTB16, PLZF) increased calcification of VIC after osteogenic stimulation. Analysis with qPCR and shotgun proteomics suggested a proosteogenic role of ZBTB16 in the early stages of osteogenic differentiation.

• Seim, Bjørn Edvard; Holt, Margrethe Flesvig; Ratajska, Aleksandra; Michelsen, Annika Elisabet; Ringseth, Monica Myklebust & Halvorsen, Bente [Show all 14 contributors for this article] (2022). Markers of extracellular matrix remodeling and systemic inflammation in patients with heritable thoracic aortic diseases. Frontiers in Cardiovascular Medicine. 9, p. 1–9. doi: 10.3389/fcvm.2022.1073069. Full text in Research Archive Show summary

  Background: In approximately 20% of patients with thoracic aortic aneurysms or dissections a heritable thoracic aortic disease (HTAD) is suspected. Several monogenic connective tissue diseases imply high risk of aortic disease, including both non-syndromic and syndromic forms. There are some studies assessing inflammation and extracellular matrix remodeling in patients with non-hereditary aortic disease, but such studies in patients with hereditary diseases are scarce.<p> <p>Aims: To quantify markers of extracellular matrix (ECM) and inflammation in patients with vascular connective tissue diseases versus healthy controls. <p>Methods: Patients with Loeys-Dietz syndrome (LDS, n = 12), Marfan syndrome (MFS, n = 11), and familial thoracic aortic aneurysm 6 (FTAA6, n = 9), i.e., actin alpha 2 (ACTA2) pathogenic variants, were recruited. Exome or genome sequencing was performed for genetic diagnosis. Several markers of inflammation and ECM remodeling were measured in plasma by enzyme immunoassays. Flow cytometry of T-cell subpopulations was performed on a subgroup of patients. For comparison, blood samples were drawn from 14 healthy controls. <p>Results: (i) All groups of HTAD patients had increased levels matrix metalloproteinase-9 (MMP-9) as compared with healthy controls, also in adjusted analyses, reflecting altered ECM remodeling. (ii) LDS patients had increased levels of pentraxin 3 (PTX3), reflecting systemic inflammation. (iii) LDS patients have increased levels of soluble CD25, a marker of T-cell activation. <p>Conclusion: Our data suggest that upregulated MMP-9, a matrix degrading enzyme, is a common feature of several subgroups of HTAD. In addition, LDS patients have increased levels of PTX3 reflecting systemic and in particular vascular inflammation.

• Törnudd, Mattias; Ghraoui, Mohamad Rodwan Al; Wahlgren, Sofia; Björkman, Erik; Berg, Sören & Kvitting, John-Peder [Show all 8 contributors for this article] (2022). Quantification of platelet function - a comparative study of venous and arterial blood using a novel flow cytometry protocol. Platelets. ISSN 0953-7104. doi: 10.1080/09537104.2021.2019209. Full text in Research Archive Show summary

  Studies of platelet function in surgical patients often involve both arterial and venous sampling. Possible effects of different sampling sites could be important, but have not been thoroughly investigated. We aimed to compare platelet function in arterial and venous blood samples using a novel flow cytometry protocol and impedance aggregometry. Arterial and venous blood was collected before anesthesia in 10 patients undergoing cardiac surgery of which nine was treated with acetylsalicylic acid until the day before surgery. Flow cytometry included simultaneous analysis of phosphatidylserine exposure, active conformation of the fibrinogen receptor (PAC-1 binding), α-granule and lysosomal release (P-selectin and LAMP-1 exposure) and mitochondrial membrane integrity. Platelets were activated with ADP or peptides activating thrombin receptors (PAR1-AP/PAR4-AP) or collagen receptor GPVI (CRP-XL). Leukocyte-platelet conjugates and P-selectin exposure were evaluated immediately in fixated samples. For impedance aggregometry (Multiplate®), ADP, arachidonic acid, collagen and PAR1-AP (TRAP) were used as activators. Using impedance aggregometry and in 27 out of 37 parameters studied with flow cytometry there was no significant difference between venous and arterial blood sampling. Arterial blood showed more PAC-1 positive platelets when activated with PAR1-AP or PAR4-AP and venous blood showed more monocyte-platelet and neutrophil-platelet conjugates and higher phosphatidylserine exposure with CRP-XL alone and combined with PAR1-AP or PAR4-AP. We found no differences using impedance aggregometry. In conclusion, testing of platelet function by flow cytometry and impedance aggregometry gave comparable results for most of the studied parameters in venous and arterial samples. Flow cytometry identified differences in PAC-1 binding when activated with PAR1-AP, exposure of phosphatidyl serine and monocyte/neutrophil-platelet conjugates, which might reflect differences in blood sampling technique or in flow conditions in this patient cohort with coronary artery disease. These differences might be considered when comparing data from different sample sites, but caution should be exercised if a different protocol is used or another patient group is studied.

• Bogdanova, Mariia; Zabirnyk, Arsenii; Malashicheva, Anna; Semenova, Daria; Kvitting, John-Peder & Kaljusto, Mari-Liis [Show all 12 contributors for this article] (2022). Models and Techniques to Study Aortic Valve Calcification in Vitro, ex Vivo and in Vivo. An Overview. Frontiers in Pharmacology. 13. doi: 10.3389/fphar.2022.835825. Full text in Research Archive Show summary

  Aortic valve stenosis secondary to aortic valve calcification is the most common valve disease in the Western world. Calcification is a result of pathological proliferation and osteogenic differentiation of resident valve interstitial cells. To develop non-surgical treatments, the molecular and cellular mechanisms of pathological calcification must be revealed. In the current overview, we present methods for evaluation of calcification in different ex vivo , in vitro and in vivo situations including imaging in patients. The latter include echocardiography, scanning with computed tomography and magnetic resonance imaging. Particular emphasis is on translational studies of calcific aortic valve stenosis with a special focus on cell culture using human primary cell cultures. Such models are widely used and suitable for screening of drugs against calcification. Animal models are presented, but there is no animal model that faithfully mimics human calcific aortic valve disease. A model of experimentally induced calcification in whole porcine aortic valve leaflets ex vivo is also included. Finally, miscellaneous methods and aspects of aortic valve calcification, such as, for instance, biomarkers are presented.

• Dumont, Karl-Andreas; Aguilera, Hans Martin; Persson, Robert; Prot, Victorien Emile; Kvitting, John-Peder & Urheim, Stig (2022). Mitral Annular Elasticity Determines Severity of Regurgitation in Barlow's Mitral Valve Disease. Journal of the American Society of Echocardiography. ISSN 0894-7317. 35(10), p. 1037–1046. doi: 10.1016/j.echo.2022.07.001. Full text in Research Archive
• Bugge, Anders; Kvitting, John-Peder; Sundset, Arve & Birkeland, Sigurd (2021). Lung autotransplantation and extra-anatomic bypass to treat an aortobronchial fistula after previous surgery for aortic coarctation. Journal of Cardiac Surgery. ISSN 0886-0440. 36(8), p. 2924–2927. doi: 10.1111/jocs.15660. Full text in Research Archive
• Kvitting, John-Peder; Beitnes, Jan Otto & Lundblad, Runar (2021). Early results after aortic annuloplasty with a complete external Dacron band. General Thoracic and Cardiovascular Surgery. ISSN 1863-6705. doi: 10.1007/s11748-021-01695-1. Full text in Research Archive
• Soknes, Maria; Lingaas, Per Snorre; Lundblad, Runar & Kvitting, John-Peder (2021). Total aortic arch replacement using the thoraflex hybrid prosthesis: early- and medium-term results from a Scandinavian center. Scandinavian Cardiovascular Journal. ISSN 1401-7431. doi: 10.1080/14017431.2021.1970800. Full text in Research Archive
• Törnudd, Mattias; Ramström, Sofia; Kvitting, John-Peder; Alfredsson, Joakim; Pihl, Richard & Berg, Sören (2020). Protamine stimulates platelet aggregation in vitro with activation of the fibrinogen receptor and alpha-granule release, but impairs secondary activation via ADP and thrombin receptors. Platelets. ISSN 0953-7104. p. 90–96. doi: 10.1080/09537104.2020.1719992. Full text in Research Archive
• Zabirnyk, Arsenii; Ferrer, Miguel David; Bogdanova, Mariia; Perez, MM; Salcedo, C & Kaljusto, Mari-Liis [Show all 10 contributors for this article] (2019). SNF472, a novel anti-crystallization agent, inhibits induced calcification in an in vitro model of human aortic valve calcification. Vascular pharmacology. ISSN 1537-1891. p. 1–7. doi: 10.1016/j.vph.2019.106583. Full text in Research Archive Show summary

  The purpose of the present study was to investigate whether SNF472, the hexasodium salt of myo-inositol hexaphosphate (IP6 or phytate): 1. Inhibits induced calcification in cultured aortic valve interstitial cells (VIC) as an in vitro model of aortic valve stenosis and 2. Whether inhibition is different in VIC obtained from healthy and calcified aortic valves. VIC from healthy (n = 5) and calcified (n = 7) human aortic valves were seeded in basic growth medium, osteogenic differentiation medium alone, or in osteogenic medium with SNF472 (3, 10, and 30 μM) and cultivated for 3 weeks. Calcification was quantified spectrophotometrically after Alizarin Red staining. In VIC from calcified valves, a complete inhibition of calcification was observed with SNF472 concentrations of 10 and 30 μM (p < .01), significantly stronger than in VIC from healthy valves. When SNF472 was added to VIC after 1 week in osteogenic medium, 30 and 100 μM SNF472 inhibited the progression of ongoing calcification by 81 and 100% (p < .01), respectively. The same concentrations of SNF472 given after 2 weeks reduced calcification by 35 and 40% respectively (not significant). SNF472 inhibited both the formation and the progression of calcification with the strongest effect in VIC from calcified valves.

• Bothe, Wolfgang; Kvitting, John Peder Escobar; Rausch, Manuel K; Timek, Tomasz A; Swanson, Julia C & Liang, David H [Show all 10 contributors for this article] (2019). Do annuloplasty rings designed to treat ischemic/functional mitral regurgitation alter left-ventricular dimensions in the acutely ischemic ovine heart? Journal of Thoracic and Cardiovascular Surgery. ISSN 0022-5223. p. 1–11. doi: 10.1016/j.jtcvs.2018.12.077. Full text in Research Archive
• Bogdanova, Mariia; Zabirnyk, Arsenii; Malashicheva, Anna; Zihlavnikova, Katarina; Karlsen, Tommy Aleksander & Kaljusto, Mari-Liis [Show all 13 contributors for this article] (2019). Interstitial cells in calcified aortic valves have reduced differentiation potential and stem cell-like properties. Scientific Reports. 9:12934, p. 1–13. doi: 10.1038/s41598-019-49016-0. Full text in Research Archive Show summary

  Valve interstitial cells (VICs) are crucial in the development of calcific aortic valve disease. The purpose of the present investigation was to compare the phenotype, differentiation potential and stem cell-like properties of cells from calcified and healthy aortic valves. VICs were isolated from human healthy and calcified aortic valves. Calcification was induced with osteogenic medium. Unlike VICs from healthy valves, VICs from calcified valves cultured without osteogenic medium stained positively for calcium deposits with Alizarin Red confirming their calcific phenotype. Stimulation of VICs from calcified valves with osteogenic medium increased calcification (p = 0.02), but not significantly different from healthy VICs. When stimulated with myofibroblastic medium, VICs from calcified valves had lower expression of myofibroblastic markers, measured by flow cytometry and RT-qPCR, compared to healthy VICs. Contraction of collagen gel (a measure of myofibroblastic activity) was attenuated in cells from calcified valves (p = 0.04). Moreover, VICs from calcified valves, unlike cells from healthy valves had lower potential to differentiate into adipogenic pathway and lower expression of stem cell-associated markers CD106 (p = 0.04) and aldehyde dehydrogenase (p = 0.04). In conclusion, VICs from calcified aortic have reduced multipotency compared to cells from healthy valves, which should be considered when investigating possible medical treatments of aortic valve calcification.

• Ha, Hojin; Kvitting, John Peder Escobar; Dyverfeldt, Petter & Ebbers, Tino (2019). 4D Flow MRI quantification of blood flow patterns, turbulence and pressure drop in normal and stenotic prosthetic heart valves. Magnetic Resonance Imaging. ISSN 0730-725X. 55, p. 118–127. doi: 10.1016/j.mri.2018.09.024. Full text in Research Archive
• Holt, Margrethe Flesvig; Seim, Bjørn Edvard; Øgaard, Jonas; Olsen, Maria Belland; Woldbæk, Per R & Kvitting, John Peder Escobar [Show all 12 contributors for this article] (2019). Selective and marked decrease of complement receptor C5aR2 in human thoracic aortic aneurysms: A dysregulation with potential inflammatory effects. Open heart. 6.e001098(2), p. 1–8. doi: 10.1136/openhrt-2019-001098. Full text in Research Archive Show summary

  <i>Objective</i> - The aetiology of thoracic aortic aneurysm (TAA) is largely unknown, but inflammation is likely to play a central role in the pathogenesis. In this present study, we aim to investigate the complement receptors in TAA.<p> <p><i>Methods</i> - Aortic tissue and blood from 31 patients with non-syndromic TAA undergoing thoracic aortic repair surgery were collected. Aortic tissue and blood from 36 patients with atherosclerosis undergoing coronary artery bypass surgery or aortic valve replacement were collected and served as control material. The expression of the complement anaphylatoxin receptors C3aR1, C5aR1 and C5aR2 in aortic tissue were examined by quantitative RT-PCR and C5aR2 protein by immunohistochemistry. Colocalisation of C5aR2 to different cell types was analysed by immunofluorescence. Complement activation products C3bc and sC5b-9 were measured in plasma.<p> <p><i>Results</i> - Compared with controls, TAA patients had substantial (73%) downregulated gene expression of C5aR2 as seen both at the mRNA (p=0.005) level and protein (p=0.03) level. In contrast, there were no differences in the expression of C3aR1 and C5aR1 between the two groups. Immunofluorescence examination showed that C5aR2 was colocalised to macrophages and T cells in the aortic media. There were no differences in the degree of systemic complement activation between the two groups.<p> <p><i>Conclusion</i> - Our findings suggest downregulation of the C5aR2, regarded to act mainly anti-inflammatory, in electively operated TAA as compared with non-aneurysmatic aortas of patients with aortic stenosis and/or coronary artery disease. This may tip the balance towards a relative increase in the inflammatory responses induced by C5aR1 and thus enhance the inflammatory processes in TAA.

• Kvitting, John Peder Escobar; Nielsen, Niels-Erik; Vanhanen, Ingemar & Baranowski, Jacek (2018). Surgical management of outflow tract obstruction after transapical mitral valve implantation. Journal of Cardiac Surgery. ISSN 0886-0440. 33(9), p. 545–547. doi: 10.1111/jocs.13771. Full text in Research Archive
• Dumont, Karl-Andreas; Kvitting, John Peder Escobar; Karlsen, Jørn S.; Remme, Espen W.; Hausken, John & Lundblad, Runar [Show all 8 contributors for this article] (2018). Validation of a holographic display for quantification of mitral annular dynamics by three-dimensional echocardiography. Journal of the American Society of Echocardiography. ISSN 0894-7317. p. 1–18. doi: 10.1016/j.echo.2018.08.010. Full text in Research Archive
• Kvitting, John Peder Escobar; Hermansson, Ulf & Vanhanen, Ingemar (2018). Resection of a plasma cell granuloma combining a conventional posterolateral left-sided thoracotomy with a minimally invasive valve approach. General Thoracic and Cardiovascular Surgery. ISSN 1863-6705. p. 1–3. doi: 10.1007/s11748-018-0986-y. Full text in Research Archive
• Bogdanova, Mariia; Kostina, Aleksandra; Zihlavnikova, Katarina; Zabirnyk, Arsenii; Malashicheva, Anna & Stensløkken, Kåre-Olav [Show all 12 contributors for this article] (2018). Inflammation and Mechanical Stress Stimulate Osteogenic Differentiation of Human Aortic Valve Interstitial Cells. Frontiers in Physiology. 9. doi: 10.3389/fphys.2018.01635. Full text in Research Archive Show summary

  Background: Aortic valve calcification is an active proliferative process, where interstitial cells of the valve transform into either myofibroblasts or osteoblast-like cells causing valve deformation, thickening of cusps and finally stenosis. This process may be triggered by several factors including inflammation, mechanical stress or interaction of cells with certain components of extracellular matrix. The matrix is different on the two sides of the valve leaflets. We hypothesize that inflammation and mechanical stress stimulate osteogenic differentiation of human aortic valve interstitial cells (VICs) and this may depend on the side of the leaflet. Methods: Interstitial cells isolated from healthy and calcified human aortic valves were cultured on collagen or elastin coated plates with flexible bottoms, simulating the matrix on the aortic and ventricular side of the valve leaflets, respectively. The cells were subjected to 10% stretch at 1 Hz (FlexCell bioreactor) or treated with 0.1 μg/ml lipopolysaccharide, or both during 24 h. Gene expression of myofibroblast- and osteoblast-specific genes was analyzed by qPCR. VICs cultured in presence of osteogenic medium together with lipopolysaccharide, 10% stretch or both for 14 days were stained for calcification using Alizarin Red. Results: Treatment with lipopolysaccharide increased expression of osteogenic gene bone morphogenetic protein 2 (BMP2) (5-fold increase from control; p = 0.02) and decreased expression of mRNA of myofibroblastic markers: α-smooth muscle actin (ACTA2) (50% reduction from control; p = 0.0006) and calponin (CNN1) (80% reduction from control; p = 0.0001) when cells from calcified valves were cultured on collagen, but not on elastin. Mechanical stretch of VICs cultured on collagen augmented the effect of lipopolysaccharide. Expression of periostin (POSTN) was inhibited in cells from calcified donors after treatment with lipopolysaccharide on collagen (70% reduction from control, p = 0.001), but not on elastin. Lipopolysaccharide and stretch both enhanced the pro-calcific effect of osteogenic medium, further increasing the effect when combined for cells cultured on collagen, but not on elastin. Conclusion: Inflammation and mechanical stress trigger expression of osteogenic genes in VICs in a side-specific manner, while inhibiting the myofibroblastic pathway. Stretch and lipopolysaccharide synergistically increase calcification.

• Ha, Hojin; Kvitting, John Peder Escobar; Dyverfeldt, Petter & Ebbers, Tino (2017). Validation of pressure drop assessment using 4D flow MRI-based turbulence production in various shapes of aortic stenoses. Magnetic Resonance in Medicine. ISSN 0740-3194. 81(2), p. 893–906. doi: 10.1002/mrm.27437. Full text in Research Archive
• Johansson, Mats J; Kvitting, John Peder Escobar; Flatebø, Torun; Nicolaysen, Anne; Nicolaysen, Gunnar & Walther, Sten M (2016). Inhibition of constitutive nitric oxide synthase does not influence ventilation-perfusion matching in normal prone adult sheep with mechanical ventilation. Anesthesia and Analgesia. ISSN 0003-2999. 123(6), p. 1492–1499. doi: 10.1213/ANE.0000000000001556. Full text in Research Archive
• Kvitting, John Peder Escobar & Geiran, Odd (2016). Karl Viktor Hall: From In Situ Vein Bypass to the Tilting Disc Heart Valve Prosthesis. Annals of Thoracic Surgery. ISSN 0003-4975. 102(5), p. 1756–1761. doi: 10.1016/j.athoracsur.2016.03.120. Full text in Research Archive

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• Bergh, Julie; Bugge, Cecilie; Aabel, Eivind Westrum; Hopp, Einar; Hasselberg, Nina Eide & Kvitting, John-Peder [Show all 8 contributors for this article] (2026). Fast non-sustained ventricular tachycardias predict life threatening ventricular arrhythmias in patients with mitral valve prolapse monitored by implantable loop recorder. doi: 10.1093/europace/euag105.1006. Full text in Research Archive Show summary

  Abstract Background A subset of patients with mitral valve prolapse (MVP) have ventricular arrhythmias originating from papillary muscles and the mitral ring and are defined as arrhythmic MVP (AMVP). Non-sustained ventricular tachycardia (NSVT) during follow-up is found to be predictive of severe ventricular arrhythmias (VA); however, the impact of NSVT rate is less documented. Prospective studies using continuous rhythm monitoring in AMVP patients with LGE data are scarce. Purpose We aimed to evaluate the presence of fast NSVTs and LGE on cardiac magnetic resonance (CMR) as prognostic factors for severe VA in patients with AMVP continuously rhythm monitored with an implantable loop recorder (ILR). Methods We included AMVP patients without previous severe VA for prospective VA monitoring with ILR implanted at inclusion. NSVT was defined as ≥ 3 consecutive beats with heart rate &gt; 100 beats per minute (bpm). We recorded the number of NSVTs below and above rate of 180 bpm with fast NSVT defined as rate &gt; 180 bpm. Life threatening VA was defined as aborted cardiac arrest, appropriate treatment by primary preventive implantable cardioverter-defibrillator, sustained ventricular tachycardia or NSVT with hemodynamic instability. CMR with LGE was performed within 18 months after inclusion. Results 52 patients (71 % female, mean age 48 ±16 years) were monitored with ILR for a mean duration of 36 ± 6 months. Severe VA occurred in six patients during follow-up. Five of six patients (83%) with severe VA had fast NSVT during follow-up, and fast NSVT predicted severe VA with OR 15.91 (95% CI 1.67-151.15, P=0.02). Also, a higher number of fast NSVTs predicted risk of severe VA (OR 1.63, [95% CI 1.08-2.46], P=0.02.) Presence of NSVT &lt; 180 bpm and the number of NSVTs &lt; 180 bpm were not associated with severe VA (P&gt;0.05). 41 patients underwent CMR with LGE present in 7 (17%) patients. Of the 6 patients with severe VA, 5 underwent LGE-evaluation, and 3/5 (60%) had LGE present on CMR with an association between presence of LGE and severe VA with an OR of 12.00 (95% CI 1.52-95.03, P=0.02). Patients with LGE had a higher number of NSVTs &gt; 180 bpm compared to those without (incidence rate ratio 3.89, [95% CI 1.02-14.83], P=0.048). Conclusion Fast NSVT with rate &gt; 180 bpm predicted severe VA in AMVP patients prospectively monitored with ILR while NSVT with rate &lt; 180 bpm did not. Presence of LGE was associated with severe VA and a higher number of fast NSVTs. These results support NSVT &gt; 180 bpm as an important risk marker in patients with AMVP.

• Kvitting, John-Peder; Lindenskov, Paal Helge H. & MOENE, KALLE (2024). Supersoniske passasjerfly, Ødipusfellen og snuvegring. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 144(4), p. 1–7. doi: 10.4045/tidsskr.24.0021. Full text in Research Archive
• Kvitting, John-Peder; Lindenskov, Paal Helge H. & Moene, Kalle (2022). Sorte svaner og fete haler. 142(18), p. 1–14. doi: 10.4045/tidsskr.22.0496. Full text in Research Archive
• Kvitting, John-Peder; Koul, Bansi & Geiran, Odd (2022). Bjarne K. H. Semb: The contriver of the first implantation of a total artificial heart in Europe. Artificial Organs. ISSN 0160-564X. 46(7), p. 1221–1226. doi: 10.1111/aor.14252. Full text in Research Archive
• Kvitting, John-Peder; Eek, Christian; Andreassen, Arne K. & Lundblad, Runar (2022). Thrombus formation in the noncoronary sinus of Valsalva following primary graft dysfunction. Journal of Cardiac Surgery. ISSN 0886-0440. doi: 10.1111/jocs.16482. Full text in Research Archive Show summary

  We hereby present a case of thrombus formation in the noncoronary sinus of Valsalva following primary graft dysfunction. The case highlights that stagnant and nonpulsatile flow can form thrombi in the noncoronary sinus since this sinus does not have a natural distal runoff.

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