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Impact of underlying heart disease per se on the utility of preoperative NT-proBNP in adult cardiac surgery
Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery. Sun Yat Sen Univ, Peoples R China.ORCID iD: 0000-0003-4173-8565
Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
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2018 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 2, article id e0192503Article in journal (Refereed) Published
Abstract [en]

Objective The primary aim was to investigate the role of underlying heart disease on preoperative NT-proBNP levels in patients admitted for adult cardiac surgery, after adjusting for the known confounders age, gender, obesity and renal function. The second aim was to investigate the predictive value of preoperative NT-proBNP with regard to severe postoperative heart failure (SPHF) and postoperative mortality. Methods A retrospective cohort study based on preoperative NT-proBNP measurements in an unselected cohort including all patients undergoing first time surgery for coronary artery disease (CAD; n = 2226), aortic stenosis (AS; n = 406) or mitral regurgitation (MR; n = 346) from April 2010 to August 2016 in the southeast region of Sweden (n = 2978). Concomitant procedures were not included, with the exception of Maze or tricuspid valve procedures. Results Preoperative NT-proBNP was 1.67 times (pamp;lt;0.0001) and 1.41 times (pamp;lt;0.0001) higher in patients with AS or MR respectively, than in patients with CAD after adjusting for confounders. NT-proBNP demonstrated significant discrimination with regard to SPHF in CAD (AUC = 0.79, 95% CI 0.73 +/- 0.85, pamp;lt;0.0001), MR (AUC = 0.80, 95% CI 0.72 +/- 0.87, pamp;lt;0.0001) and AS (AUC = 0.66, 95% CI 0.51 +/- 0.81, p = 0.047). In CAD patients NT-proBNP demonstrated significant discrimination with regard to postoperative 30-day or in-hospital mortality (AUC = 0.78; 95% CI 0.71 +/- 0.85, pamp;lt;0.0001). The number of deaths was too few in the AS and MR group to permit analysis. Elevated NT-proBNP emerged as an independent risk factor for SPHF, and postoperative mortality in CAD. Conclusions Patients with AS or MR have higher preoperative NT-proBNP than CAD patients even after adjusting for confounders. The predictive value of NT-proBNP with regard to SPHF was confirmed in CAD and MR patients but was less convincing in AS patients.

Place, publisher, year, edition, pages
PUBLIC LIBRARY SCIENCE , 2018. Vol. 13, no 2, article id e0192503
National Category
Cardiac and Cardiovascular Systems
Identifiers
URN: urn:nbn:se:liu:diva-145771DOI: 10.1371/journal.pone.0192503ISI: 000424517900085PubMedID: 29420603OAI: oai:DiVA.org:liu-145771DiVA, id: diva2:1192475
Note

Funding Agencies|Region Ostergotland [LIO-443891]

Available from: 2018-03-22 Created: 2018-03-22 Last updated: 2019-10-29
In thesis
1. Implications of myocardial dysfunction before and after aortic valve intervention
Open this publication in new window or tab >>Implications of myocardial dysfunction before and after aortic valve intervention
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

BACKGROUND

Postoperative 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.

METHODS

This 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 dynamics

of 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.

RESULTS

Study I

This 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 II

This 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 III

This 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 IV

We 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.

CONCLUSION

Postoperative 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.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2019. p. 92
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1680
National Category
Cardiac and Cardiovascular Systems Surgery Anesthesiology and Intensive Care Gastroenterology and Hepatology
Identifiers
urn:nbn:se:liu:diva-156719 (URN)10.3384/diss.diva-156719 (DOI)9789176850794 (ISBN)
Public defence
2019-05-29, Berzeliussalen, Campus US, Linköping, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2019-05-13 Created: 2019-05-13 Last updated: 2019-05-13Bibliographically approved
2. NT-proBNP as a marker of postoperative heart failure in adult cardiac surgery
Open this publication in new window or tab >>NT-proBNP as a marker of postoperative heart failure in adult cardiac surgery
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

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.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2019. p. 79
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1712
National Category
Cardiac and Cardiovascular Systems Surgery Anesthesiology and Intensive Care Gastroenterology and Hepatology
Identifiers
urn:nbn:se:liu:diva-161324 (URN)10.3384/diss.diva-161324 (DOI)9789179299699 (ISBN)
Public defence
2019-11-28, Berzeliussalen, Campus US, Linköping, 13:00 (English)
Opponent
Supervisors
Available from: 2019-10-29 Created: 2019-10-29 Last updated: 2020-02-06Bibliographically approved

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