Diastolic dysfunction is associated with major adverse outcomes following cardiac surgery. We hypothesized that multisystem endpoints of morbidity would be higher in patients with diastolic dysfunction. A total of 142 patients undergoing cardiac surgical procedures with cardiopulmonary bypass were included in the study. Intraoperative assessments of diastolic function according to the 2016 American Society of Echocardiography and European Association of Cardiovascular Imaging guidelines using transesophageal echocardiography were performed. Cardiac Postoperative Morbidity Score (CPOMS) on days 3, 5, 8, and 15; length of stay in ICU and hospital; duration of intubation; incidence of new atrial fibrillation; 30-day major adverse cardiac and cerebrovascular events were recorded. Diastolic function was determinable in 96.7% of the dataset pre and poststernotomy assessment (n = 240). Diastolic dysfunction was present in 70.9% (n = 88) of measurements before sternotomy and 75% (n = 93) after sternal closure. Diastolic dysfunction at either stage was associated with greater CPOMS on D5 (p = 0.009) and D8 (p = 0.009), with CPOMS scores 1.24 (p = 0.01) higher than in patients with normal function. Diastolic dysfunction was also associated with longer durations of intubation (p = 0.001), ICU length of stay (p = 0.019), and new postoperative atrial fibrillation (p = 0.016, OR (95% CI) = 4.50 (1.22–25.17)). We were able to apply the updated ASE/EACVI guidelines and grade diastolic dysfunction in the majority of patients. Any grade of diastolic dysfunction was associated with greater all-cause morbidity, compared with patients with normal diastolic function.

Remote ischemic conditioning (RIC) using transient limb ischemia/reperfusion has been reported to reduce perioperative myocardial injury in patients undergoing coronary artery bypass grafting and/or valve surgery. The role of intravenous glyceryl trinitrate (GTN) therapy administered during cardiac surgery as a cardioprotective agent and whether it interferes with RIC cardioprotection is not clear and is investigated in the ERIC-GTN trial (http://www.clinicaltrials.gov: NCT01864252). The ERIC-GTN trial is a single-site, doubleblind, randomized, placebo-controlled study. Consenting adult patients (age > 18 years) undergoing elective coronary artery bypass grafting ± valve surgery with blood cardioplegia will be eligible for inclusion. Two hundred sixty patients will be randomized to 1 of 4 treatment groups following anesthetic induction: (1) RIC alone, a RIC protocol comprising three 5-minute cycles of simultaneous upper-arm and thigh cuff inflation/deflation followed by an intravenous (IV) placebo infusion; (2) GTN alone, a simulated sham RIC protocol followed by an IV GTN infusion; (3) RIC + GTN, a RIC protocol followed by an IV GTN infusion; and (4) neither RIC nor GTN, a sham RIC protocol followed by IV placebo infusion. The primary endpoint will be perioperative myocardial injury as quantified by the 72-hour area-under-the-curve serum high-sensitivity troponin T. The ERIC-GTN trial will determine whether intraoperative GTN therapy is cardioprotective during cardiac surgery and whether it affects RIC cardioprotection.

Remote ischaemic preconditioning (RIPC) using transient limb ischaemia failed to improve clinical outcomes following cardiac surgery and the reasons for this remain unclear. In the ERIC-GTN study, we evaluated whether concomitant nitrate therapy abrogated RIPC cardioprotection. We also undertook a post-hoc analysis of the ERICCA study, to investigate a potential negative interaction between RIPC and nitrates on clinical outcomes following cardiac surgery. In ERIC-GTN, 185 patients undergoing cardiac surgery were randomized to: (1) Control (no RIPC or nitrates); (2) RIPC alone; (3); Nitrates alone; and (4) RIPC + Nitrates. An intravenous infusion of nitrates (glyceryl trinitrate 1 mg/mL solution) was commenced on arrival at the operating theatre at a rate of 2–5 mL/h to maintain a mean arterial pressure between 60 and 70 mmHg and was stopped when the patient was taken off cardiopulmonary bypass. The primary endpoint was peri-operative myocardial injury (PMI) quantified by a 48-h area-under-the-curve high-sensitivity Troponin-T (48 h-AUC-hs-cTnT). In ERICCA, we analysed data for 1502 patients undergoing cardiac surgery to investigate for a potential negative interaction between RIPC and nitrates on clinical outcomes at 12-months. In ERIC-GTN, RIPC alone reduced 48 h-AUC-hs-cTnT by 37.1%, when compared to control (ratio of AUC 0.629 [95% CI 0.413–0.957], p = 0.031), and this cardioprotective effect was abrogated in the presence of nitrates. Treatment with nitrates alone did not reduce 48 h-AUC-hs-cTnT, when compared to control. In ERICCA there was a negative interaction between nitrate use and RIPC for all-cause and cardiovascular mortality at 12-months, and for risk of peri-operative myocardial infarction. RIPC alone reduced the risk of peri-operative myocardial infarction, compared to control, but no significant effect of RIPC was demonstrated for the other outcomes. When RIPC and nitrates were used together they had an adverse impact in patients undergoing cardiac surgery with the presence of nitrates abrogating RIPC-induced cardioprotection and increasing the risk of mortality at 12-months post-cardiac surgery in patients receiving RIPC.

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