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- Boano, Gabriella, et al.
(författare)
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Biochemical response to cryothermal and radiofrequency exposure of the human myocardium at surgical ablation of atrial fibrillation : a randomized controlled trial
- 2020
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Ingår i: Translational Medicine Communications. - : BioMed Central (BMC). - 2396-832X. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Background: Surgical cryothermia and radiofrequency (RF) ablations for atrial fibrillation (AF) seem to result in similar sinus rhythm restoration, but the biochemical consequences of the two methods are unclear. We aimed to compare the biochemical responses to the two ablative methods in concomitant mitral valve surgery (MVS).Methods: Sixty mitral valve surgery patients with AF were prospectively included. Forty-one patients planned for ablation were randomized to cryothermia (n = 20) or radiofrequency (n = 21) ablation and 19 served as controls. Markers for myocardial injury, inflammation, cell stress, apoptosis, and heart failure were analyzed pre- and postoperatively at different time points.Results: Troponin T and creatine kinase isoenzyme MB (CK-MB) peak levels were significantly higher in the cryothermia group compared with the RF group (12,805 [6140–15,700] vs. 2790 [1880–4180] ng/L; P = 0.002 and 271 [217–357] vs. 79 [66–93] μg/L; P < 0.001, respectively). Both groups had significantly higher levels than the no-ablation group. There were no group differences in C-reactive protein (CRP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP), but there were correlations between pre- and postoperative levels of both CRP (rs = 0.41, P = 0.001) and NT-proBNP (rs = 0.48, P < 0.001). Protease-activated receptor 1 (PAR-1) and heat shock protein 27 (HSP27) were significantly increased in the cryoablation group.Conclusions: Cryoablation results in a larger myocardial injury and possibly more elevated apoptotic activity and cell stress compared with the RF technique. The type of ablation device did not have any significant influence on the postoperative inflammatory response nor on the early postoperative levels of NT-proBNP.
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| 2. |
- Boano, Gabriella, 1974-
(författare)
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Surgical Ablation of Atrial Fibrillation with Cryo and Radiofrequency Concomitant to Mitral Valve Surgery : Clinical, Biochemical and Echocardiography Outcomes
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Atrial fibrillation (AF) is the most common arrhythmia seen in clinical practice. In cardiac surgery, the negative influence of AF on short- and long-term outcomes has made concomitant ablation procedures more common. The indications, clinical aspects, results, risks, and benefits of the additional surgical ablation are still valuable topics for discussion. This compilation thesis consists of four papers aiming to investigate some of the clinical, biochemical, and echocardiographic aspects of surgical ablation for AF (Cox-Maze IV) when performed concomitant to mitral valve surgery (MVS).Through a retrospective, case-control, single-center study, we described the impact of the Cox-Maze IV procedure added to MVS with focus on postoperative heart failure (paper I).Cryoenergy (cryo) and radiofrequency (RF) are the two different energy sources mainly used in Cox-Maze IV for AF ablation. To achieve linear scars in the atrial wall, the RF procedure uses heat damage, whereas the cryo method freezes down to -150°C. Through a prospective, randomized, longitudinal, controlled study, we compared the biochemical responses of the two ablative methods in concomitant MVS and the release of enzymes expressing myocardial injury, as well as inflammatory, cell stress, and apoptosis-specific proteins. We could show that cryo results in a larger release of markers for myocardial damage but has no impact on the early inflammatory response (paper II).Extended scar lesions resulting after maze may influence atrial function. As the left atrium plays a key role in the altered cardiac hemodynamics in AF, an echocardiographic analysis of the effects of the Cox-Maze IV procedure concomitant to MVS on the left atrium was carried out. The impacts of the two energy sources (cryo and RF) on left atrial remodeling and function had not been compared previously. Their direct effect on left atrial remodeling and mechanical function were assessed 1 year after surgery in patients with restored sinus rhythm. Sinus rhythm restoration after MVS concomitant to Cox-Maze IV results in a reduced left atrium size regardless of the energy source used. Three-dimensional echocardiography showed that, compared to RF, the extension of the ablation area produced by cryo implies major left atrium structural remodeling affecting systolic function. The negative effect on left atrium remodeling seems to be linear with the duration of the AF (paper III).An overview of the pacemaker implantation rate after the Cox-Maze IV procedure concomitant to MVS was obtained in a multicenter study using national qualitative registers (SWEDHEART, Carath, Svenska ICD- och Pacemakerregistret) (paper IV, sumbitted).Our results contribute to optimizing surgical indications and patient selection, providing a deeper understanding of the biochemical and echocardiographic changes during and after surgical ablation.
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| 3. |
- Engström, Karolina, et al.
(författare)
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Novel SMAD3 p.Arg386Thr genetic variant co-segregating with thoracic aortic aneurysm and dissection
- 2020
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Ingår i: Molecular Genetics & Genomic Medicine. - : John Wiley & Sons. - 2324-9269. ; 8:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Pathogenic variants in the SMAD3 gene affecting the TGF-beta/SMAD3 signaling pathway with aortic vessel involvement cause Loeys-Dietz syndrome 3, also known as aneurysms-osteoarthritis syndrome.Methods: Description of clinical history of a family in Sweden using clinical data, DNA sequencing, bioinformatics, and pedigree analysis.Results: We report a novel SMAD3 variant, initially classified as a genetic variant of uncertain clinical significance (VUS), and later found to be co-segregating with aortic dissection in the family. The index patient presented with a dissecting aneurysm of the aorta including the ascending, descending, and abdominal parts. Genotype analysis revealed a heterozygous missense SMAD3 variant: NM_005902.3(SMAD3): c.11576G > C (p.Arg386Thr). The same variant was also identified in a 30 years old formalin-fixed paraffin-embedded block of tissue from a second cousin, who died at 26 years of age from a dissecting aneurysm of the aorta.Conclusion: A "variant of uncertain significance" according to the ACMG guidelines has always a scope for reappraisal. Genetic counselling to relatives, and the offering of surveillance service is important to families with aortic aneurysm disease. The report also highlight the potential use of FFPE analysis from deceased relatives to help in the interpretation of variants.
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| 6. |
- Hultkvist, Henrik, 1968-
(författare)
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Implications of myocardial dysfunction before and after aortic valve intervention
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- BACKGROUNDPostoperative heart failure in the setting of aortic valve surgery results in poor long-term survival. We hypothesized that there could be a myocardial factor that is not addressed by risk scores currently available. We speculated that this myocardial factor could be diastolic dysfunction. By evaluating postoperative heart failure, the EuroSCORE, the NT-proBNP level, and diastolic function, we might achieve a deeper understanding of the outcome for individuals with postoperative heart failure.METHODSThis research project was built upon four cohort studies. The first two studies (I and II) were retrospective in nature, and studies III and IV were prospective, observational, and longitudinal. All work was based on data from clinical and national databases. In Study I, we compared the outcome of patients with or without postoperative heart failure, evaluated according to the preoperative risk score. In Study II, we explored the effect of underlying heart disease on the preoperative level of NT-proBNP and the relationships between NT-proBNP and severe postoperative heart failure and short-term mortality. In Study III, we described the dynamicsof NT-proBNP, from a preoperative evaluation to a six-month follow-up, in patients that underwent one of two different procedures: a surgical aortic valve replacement and a transcatheter implantation. We related both pre- and postprocedural NT-proBNP levels to one-year mortality. In Study IV, we evaluated diastolic function in patients that underwent surgical aortic valve replacement and its influence on outcome. We also evaluated NT-proBNP levels and postoperative heart failure as predictors of long-term mortality.RESULTSStudy IThis study included 397 patients that underwent isolated surgical aortic valve replacements. Of these, 45 patients (11%) were treated for postoperative heart failure. With an average follow-up of 8.1 years (range 5.2-11.2), among patients at low risk (EuroSCORE≤7), the crude five-year survival rates were 58% in patients with postoperative heart failure and 89% in those without postoperative heart failure (p<0.001). Among patients with postoperative heart failure, those classified as low risk had the same poor long-term prognosis as those classified as high risk (EuroSCORE>7). In the high risk group, survival rates were similar between patients with or without postoperative heart failure (57% vs. 64%; p=0.60).Study IIThis study included a cohort of 2978 patients with coronary artery disease, aortic stenosis, and mitral regurgitation. Preoperative NTproBNP levels were found to be 1.7-fold higher in patients with aortic stenosis than in patients with coronary artery disease and 1.4-fold higher in patients with mitral regurgitation than in patients with coronary disease. The power of preoperative NT-proBNP for predicting severe postoperative heart conditions was good among patients with coronary heart disease and patients with mitral regurgitation, but not as good among patients with aortic stenosis. NT-proBNP also showed good discriminating power for short-term mortality among patients with coronary artery disease. Moreover, NT-proBNP was found to be an independent predictor for both severe postoperative heart failure and short-term mortality in patients with coronary artery disease.Study IIIThis study included 462 patients that underwent preoperative evaluations for aortic valve disease. Aortic valve interventions elicited a rise in NT-proBNP that was more pronounced in patients undergoing surgical aortic valve replacement compared to patients undergoing transcatheter valve implantation. No deterioration in NT-proBNP was observed during the waiting time before the intervention, despite a median duration of four months. At six months after the intervention, NT-proBNP levels had decreased to or below the preoperative levels in all groups. Among patients that received surgical aortic valve replacements, pre-and early postoperative NT-proBNP levels showed good discriminatory power for oneyear mortality. This discriminatory power was not observed among patients that had undergone a transcatheter procedure; those patients had higher levels of both pre- and postoperative NT-proBNP compared to patients that had undergone surgery.Study IVWe evaluated 273 patients that underwent aortic valve surgery. High left ventricular filling pressure was present in 22% (n=54) of patients at the time of surgery. At six months after surgery, diastolic function deteriorated in 24/193 (12%) patients and improved in 27/54 (50%) patients. Diastolic dysfunction was not found to be associated with long-term mortality. However, both postoperative heart failure and preoperative NTproBNP levels were associated with increases in long-term mortality. In a multivariable Cox analysis, NT-proBNP remained predictive of long-term mortality.CONCLUSIONPostoperative heart failure contributed to long-term mortality, even in patients considered to be at low risk preoperatively. Our results suggested that pressure overload, followed by a volume overload led to a NTproBNP response that was more pronounced than the ischemia response. Elevated levels of NT-proBNP were associated with both short- and long-term mortality. In these studies, we could not corroborate the notion that high left ventricular filling pressure was associated with long-term mortality.
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| 7. |
- Jiang, Huiqi, et al.
(författare)
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NT-proBNP and postoperative heart failure in surgery for aortic stenosis
- 2019
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Ingår i: Open heart. - : BMJ Publishing Group Ltd. - 2053-3624. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Objective Postoperative heart failure (PHF) after aortic valve replacement (AVR) for aortic stenosis (AS) may initially appear mild and transient but has serious long-term consequences. Methods to assess PHF are not well documented. We studied the association between N-terminal pro-B-type natriuretic peptide (NT-proBNP) and PHF after AVR for AS.Methods This is a prospective, observational, longitudinal study of 203 patients undergoing elective first-time AVR for AS. Plasma NT-proBNP was assessed at preoperative evaluation, the day before surgery, and the first (POD1) and third postoperative morning. A clinical endpoints committee, blinded to NT-proBNP results, used prespecified haemodynamic criteria to diagnose PHF. The mean follow-up was 8.6±1.1 years.Results No patient with PHF (n=18) died within 30 days after surgery, but PHF was associated with poor long-term survival (HR 3.01, 95% CI 1.45 to 6.21, p=0.003). NT-proBNP was significantly higher in patients with PHF only on POD1 (6415 (3145–11 220) vs 2445 (1540–3855) ng/L, p<0.0001). NT-proBNP POD1 provided good discrimination of PHF (area under the curve=0.82, 95% CI 0.72 to 0.91, p<0.0001; best cut-off 5290 ng/L: sensitivity 63%, specificity 85%). NT-proBNP POD1 ≥5290 ng/L identified which patients with PHF carried a risk of poor long-term survival, and PHF with NT-proBNP POD1 ≥ 5290 ng/L emerged as a risk factor for long-term mortality in the multivariable Cox regression (HR 6.20, 95% CI 2.72 to 14.1, p<0.0001).Conclusions The serious long-term consequences associated with PHF after AVR for AS were confirmed. NT-proBNP level on POD1 aids in the assessment of PHF and identifies patients at particular risk of poor long-term survival.
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| 8. |
- Jiang, Huiqi, 1981-
(författare)
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NT-proBNP as a marker of postoperative heart failure in adult cardiac surgery
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Postoperative heart failure (PHF) remains the major cause of mortality after cardiac surgery. Unfortunately, generally accepted diagnostic criteria for PHF are lacking. This may explain why the evidence for the efficacy and safety of current treatment of PHF with inotropes is insufficient. In cardiology practice N-terminal pro-B-type natriuretic peptide (NT-proBNP) is an established biomarker for heart failure. However, the association between NT-proBNP and PHF after cardiac surgery needs further clarification. Glutamate is a key intermediate in myocardial metabolism, which may improve myocardial tolerance to ischemia and facilitate post-ischemic recovery. Glutamate was associated with a reduced risk of developing severe PHF in high-risk patients undergoing coronary artery bypass surgery (CABG). The aim of this thesis was to study the role of NT-proBNP for prediction and assessment of PHF in cardiac surgery (Paper I-III) and the impact of intravenous glutamate infusion on postoperative NTproBNP after CABG (Paper IV).Paper I: We retrospectively studied the role of underlying heart disease for preoperative NT-proBNP in patients admitted for first time CABG (n=2226), aortic valve surgery (AVR) for aortic stenosis (AS) (n=406) and mitral valve surgery for mitral valve regurgitation (MR) (n=346) by adjusting for non-cardiac confounders (age, gender, obesity and renal function). The level of NT-proBNP in AS or MR was 1.67 (p<0.0001) and 1.41 times (p<0.0001) higher respectively than in coronary artery disease (CAD) after adjusting for confounders. Preoperative NT-proBNP was predictive of severe PHF in CAD and MR patients but less so in AS patients. Preoperative NT-proBNP emerged as an independent risk factor for severe PHF and postoperative mortality in CAD patients.Paper II-III: We prospectively studied the association between postoperative NT-proBNP and PHF in two cohorts, patients undergoing AVR for AS (n=203) and patients undergoing isolated CABG for acute coronary syndrome (ACS) from the GLUTAMICS-trial (n=382). NT-proBNP was measured preoperatively, on the first (POD1) and third postoperative morning (POD3). An end-points committee blinded to NT-proBNP used prespecified criteria to diagnose PHF and its severity. After AVR for AS only NT-proBNP level on POD1 provided good discrimination of PHF. PHF with NT-proBNP POD1 ≥ 5290 ng•L-1 emerged as an independent risk factor for long-term mortality (Paper II). After isolated CABG for ACS both absolute postoperative levels on POD1 and POD3 and postoperative increases of NT-proBNP were associated with PHF and the levels reflected the severity of PHF (Paper III).Paper IV: We prospectively studied the impact of intravenous glutamate infusion on postoperative NT-proBNP in a randomized double-blind study on patients undergoing CABG for ACS from the GLUTAMICS-trial (n=399). Patients were randomly allocated to intravenous infusion of L-glutamate (n=200) or saline (n=199). No effect of glutamate on postoperative NT-proBNP levels was detected in the whole cohort. According to post-hoc analysis glutamate was associated with less increase of NT-proBNP from preoperative level to POD3 and significantly lower absolute levels on POD3 among high risk patients with EuroSCORE II ≥4.15 (upper quartile).Conclusion: Patients with AS or MR have higher preoperative NT-proBNP than CAD patients after adjusting for confounders. The predictive value of NT-proBNP with regard to severe PHF and postoperative mortality was confirmed in CAD patients. Postoperative NTproBNP may prove a useful tool for assessment of PHF after AVR for AS and isolated CABG. NT-proBNP POD1 identifies patients with PHF at risk of a poor long-term survival after AVR for AS. Intravenous infusion of glutamate may prevent or mitigate PHF in highrisk patients undergoing CABG but these results need to be confirmed.
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| 9. |
- Jiang, Huiqi, 1981-, et al.
(författare)
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The impact of glutamate infusion on postoperative NT-proBNP in patients undergoing coronary artery bypass surgery : a randomized study
- 2020
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Ingår i: Journal of Translational Medicine. - : BioMed Central. - 1479-5876. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundGlutamate, a key intermediate in myocardial metabolism, may enhance myocardial recovery after ischemia and possibly reduce the incidence and severity of postoperative heart failure in coronary artery bypass surgery (CABG). N-terminal pro-B-type natriuretic peptide (NT-proBNP) can be used to assess postoperative heart failure (PHF) after CABG. Our hypothesis was that glutamate enhances myocardial recovery in post-ischemic heart failure and, therefore, will be accompanied by a mitigated postoperative increase of NT-proBNP.MethodsSubstudy of the GLUTAmate for Metabolic Intervention in Coronary Surgery (GLUTAMICS) trial (ClinicalTrials.gov Identifier: NCT00489827) a prospective triple-center double-blind randomized clinical trial on 399 patients undergoing CABG with or without concomitant procedure for acute coronary syndrome at three Swedish Cardiac Surgery centres (Linköping, Örebro, and Karlskrona) from May 30, 2007 to November 12, 2009. Patients were randomly assigned to intravenous infusion of 0.125 M L-glutamic acid or saline (1.65 mL/kg of body weight per hour) intraoperatively and postoperatively. Plasma NT-proBNP was measured preoperatively, the first (POD1) and third postoperative morning (POD3). A Clinical Endpoints Committee, blinded to both intervention and NT-proBNP used prespecified criteria to diagnose PHF. The primary endpoints were the absolute levels of postoperative NT-proBNP and the difference between preoperative and postoperative levels of NT-proBNP.ResultsOverall no significant difference was detected in postoperative NT-proBNP levels between groups. However, in high-risk patients (upper quartile of EuroSCORE II ≥ 4.15; glutamate group n = 56; control group n = 45) glutamate was associated with significantly lower postoperative increase of NT-proBNP (POD3-Pre: 3900 [2995–6260] vs. 6745 [3455–12,687] ng•L−1, p = 0.012) and lower NT-proBNP POD3 (POD3: 4845 [3426–7423] vs. 8430 [5370–14,100] ng•L−1, p = 0.001). After adjusting for significant differences in preoperative demographics, NT-proBNP POD3 in the glutamate group was 0.62 times of that in the control group (p = 0.002). Patients in the glutamate group also had shorter ICU stay (21 [19–26] vs. 25 [22–46] h, p = 0.025) and less signs of myocardial injury (Troponin T POD3 (300 [170–500] vs. 560 [210–910] ng•L−1, p = 0.025).ConclusionsPost hoc analysis of postoperative NT-proBNP suggests that intravenous infusion of glutamate may prevent or mitigate myocardial dysfunction in high-risk patients undergoing CABG. Further studies are necessary to confirm these findings.Trial registration Swedish Medical Products Agency 151:2003/70403 (prospectively registered with amendment about this substudy filed March 17, 2007). ClinicalTrials.gov Identifier: NCT00489827 (retrospectively registered) https://clinicaltrials.gov/ct2/show/NCT00489827?term=glutamics&draw=1&rank=1
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