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.