Background: Combined valvular and coronary artery bypass grafting (CAB G) surgery requires a long period of cardioplegic arrest (CA) that predisposes the heart to ischaemiareperfusion injury, low cardiac output syndrome, reperfusion dysrhythmias, inhospital mortality and increased costs. Procedures that can reduce the duration of CA would be expected to reduce intraoperative and postoperative complications. Mehods: Adults undergoing combined valvular and CABG surgery were randomized to either coronary surgery performed on the beating heart with cardiopulmonary bypass (CPB) support followed by CA for the valvular procedure (hybrid group) or surgery with both procedures carried out under CA (conventional group). The primary outcome was a composite of in-hospital death, postoperative myocardial infarction, cardiac dysrhythmias, requirements for cardiac pacing for more than 12 hours and/or inotropic support for more than 12 hours postoperativeiy. Results: One hundred and sixty patients (80 hybrid, 80 conventional) were randomized between March 2008 and July 2012. Mean age was 66.5 years and 74% were male. Valvular procedures included aortic (61.8%) and mitral (33.1%) alone or in combination (5.l %). The primary outcome occurred in 64/80 of the conventional group patients and 67/80 of the hybrid group patients (odds ratio 1.24, 95% Cl 0.54 to 2.86, p=0.61). The CA time was, on average, 16% shorter in the hybrid group (median 98 minutes vs. 89 minutes, geometric mean ration (GMR) 0.84, 95% Cl 0.77 to 0.93 , p=0.0004), but the overall duration of CPB was on average 7% longer in the hybrid group (GMR 1.07, 95% Cl 0.98 to 1.16, p=0.12). Cardiac troponin T plasma concentrations and levels of metabolites measured in heart biopsies were similar between the two treatment groups. Conclusion: The hybrid technique reduced the CA time, but this did not result in a significant reduction in the frequency of the primary outcome. In this trial the clinical outcomes and the extent of the myocardial injury were similar between the two surgical methods.

Background: Despite the recent improvements in surgical techniques and postoperative patient care, atrial fibrillation (AF) remains the most frequent complication after cardiac surgery. Although postoperative AF is often regarded as a benign clinical condition, this arrhythmia has significant adverse effects on patient recovery and postoperative survival. Its exact pathophysiology has not yet been elucidated. The present thesis aims to analyze AF risk factors and their interaction, pre-existing histological explanatory alterations of the atrium, the AF impact on postoperative survival and the compliance of a prophylactic drug regimen. Methods: During a 10-year period, consecutive cardiac surgery cases with complete data on AF occurrence and postoperative survival were extracted. All patients were operated on for coronary or valvular surgery, with cardiopulmonary bypass (CPB). Hospital and long-term survival data were obtained from Swedish population registry. Study I) Isolated coronary artery bypass grafting (CABG, n=7056), aortic valve replacement (n=690) and their combination (n=688) were considered. Independent AF risk factors and AF effects on early and 1 year mortality were investigated. Study II) Patients affected by postoperative AF among isolated CABG patients (n=7621), valvular surgeries (n=995) and their combination (n=879) were studied. Long-term survival was obtained and prognostic factors identified. Study III) Seventy patients were randomized to on-pump (n=35) or off-pump (n=35) CABG. Samples from the right atrial appendage were collected and histology was evaluated by means of light and electronic microscopy with reference to preexistent alterations related to postoperative AF. Study IV) Cardiac surgery patients with complete data on smoking status (n=3245) were reviewed. Effects of smoking on AF development and interaction among variables were explored. Study V) CABG patients without clinical contraindications to receive oral sotalol (80 mg twice daily) and magnesium were prospectively enrolled (n = 49) and compared with a matched contemporary control CABG group (n = 844). The clinical compliance to the AF prophylactic drug regimen was tested. Results: The overall AF incidence was around 26%, subdivided into 23%, 40% and 45% for isolated CABG, valve procedures and their combined surgeries, respectively. Age was the strongest predictor of postoperative AF. Coronary disease superimposed risk factors with reference to myocardial conditions at CPB weaning. Considering the preoperative smoking condition, smokers demonstrated a reduced AF incidence compared to non-smokers (20% versus 27%, p<0.001). An interaction between smoking status and inotropic support was observed: without this interaction smoking conferred a 46% risk reduction of AF (p=0.011). At the histological level, myocyte vacuolization and nuclear derangement represented anatomical independent AF predictors (p=0.002 and p=0.016, respectively). CPB exposure was not associated to postoperative AF nor histological changes. Although, postoperative AF increases the length of hospitalization in all patient groups, it did not affect the hospital survival. However, AF independently impaired the late survival, a phenomenon seen in the CABG group only. With reference to the tested sotalolmagnesium drug regimen, only 55% of CABG patients were compliant to the treatment, with marginal effects on AF occurrence. Conclusions: In addition to age, details at the CPB weaning period, pre-existing histopathological changes, the hyperadrenergic state and catecholamines are key mechanisms in the pathophysiology of postoperative AF. In particular, the CPB period hides valuable information for timely AF prophylactic stratifications. Further, compliance effects due to patient selection should also be considered in a prophylactic therapy model. Postoperative AF increases late mortality after isolated CABG surgery, but not after valvular procedures. Although the mechanisms are unclear, our results draw the attention to possible AF recurrence after hospital discharge, indicating a strict postoperative surveillance.