Routine Protamine Administration for Bleeding in Transcatheter Aortic Valve Implantation: The ACE-PROTAVI Randomized Clinical Trial.

Importance: Vascular complications after transfemoral transcatheter aortic valve implantation (TAVI) remain an important cause of procedure-related morbidity. Routine reversal of anticoagulation with protamine at the conclusion of transfemoral TAVI could reduce complications, but data remain scarce. Objective: To evaluate the efficacy and safety of routine protamine administration after transfemoral TAVI. Design, Setting, and Participants: The ACE-PROTAVI trial was an investigator-initiated, double-blind, placebo-controlled randomized clinical trial performed at 3 Australian hospitals between December 2021 and June 2023 with a 1-year follow-up period. All patients accepted for transfemoral TAVI by a multidisciplinary heart team were eligible for enrollment. Interventions: Eligible patients were randomized 1:1 between routine protamine administration and placebo. Main Outcomes and Measures: The coprimary outcomes were the rate of hemostasis success and time to hemostasis (TTH), presented as categorical variables and compared with a χ2 test or as continuous variables as mean (SD) or median (IQR), depending on distribution. The major secondary outcome was a composite of all-cause death, major and minor bleeding complications, and major and minor vascular complications after 30 days, reported in odds ratios (ORs) with 95% CIs and P values. Results: The study population consisted of 410 patients: 199 patients in the protamine group and 211 in the placebo group. The median (IQR) patient age in the protamine group was 82 (77-85) years, and 68 of 199 patients receiving protamine (34.2%) were female. The median (IQR) patient age in the placebo group was 80 (75-85) years, and 89 of 211 patients receiving the placebo (42.2%) were female. Patients receiving up-front protamine administration had a higher rate of hemostasis success (188 of 192 patients [97.9%]) than patients in the placebo group (186 of 203 patients [91.6%]; absolute risk difference, 6.3%; 95% CI, 2.0%-10.6%; P = .006); in addition, patients receiving up-front protamine had a shorter median (IQR) TTH (181 [120-420] seconds vs 279 [122-600] seconds; P = .002). Routine protamine administration resulted in a reduced risk of the composite outcome in the protamine group (10 of 192 [5.2%]) vs the placebo group (26 of 203 [12.8%]; OR, 0.37; 95% CI, 0.1-0.8; P = .01). This difference was predominantly driven by the difference in the prevalence of minor vascular complications. There were no adverse events associated with protamine use. Conclusions and Relevance: In the ACE-PROTAVI randomized clinical trial, routine administration of protamine increased the rate of hemostasis success and decreased TTH. The beneficial effect of protamine was reflected in a reduction in minor vascular complications, procedural time, and postprocedural hospital stay duration in patients receiving routine protamine compared with patients receiving placebo. Trial Registration: anzctr.org.au Identifier: ACTRN12621001261808.

Poor Agreement Between Preoperative Transthoracic Echocardiography and Intraoperative Transesophageal Echocardiography for Grading Diastolic Dysfunction.

BACKGROUND: Guidelines for the evaluation and grading of diastolic dysfunction are available for transthoracic echocardiography (TTE). Transesophageal echocardiography (TEE) is used for this purpose intraoperatively but the level of agreement between these 2 imaging modalities for grading diastolic dysfunction is unknown. We assessed agreement between awake preoperative TTE and intraoperative TEE for grading diastolic dysfunction. METHODS: In 98 patients undergoing cardiac surgery, key Doppler measurements were obtained using TTE and TEE at the following time points: TTE before anesthesia induction (TTEawake), TTE following anesthesia induction (TTEanesth), and TEE following anesthesia induction (TEEanesth). The primary endpoint was grade of diastolic dysfunction categorized by a simplified algorithm, and measured by TTEawake and TEEanesth, for which the weighted κ statistic assessed observed agreement beyond chance. Secondary endpoints were peak early diastolic lateral mitral annular tissue velocity (e'lat) and the ratio of peak early diastolic mitral inflow velocity (E) to e'lat (E/e'lat), measured by TTEawake and TEEanesth, were compared using Bland-Altman limits of agreement. RESULTS: Disagreement in grading diastolic dysfunction by ≥1 grade occurred in 43 (54%) of 79 patients and by ≥2 grades in 8 (10%) patients with paired measurements for analysis, yielding a weighted κ of 0.35 (95% confidence interval [CI], 0.19-0.51) for the observed level of agreement beyond chance. Bland-Altman analysis of paired data for e'lat and E/e'lat demonstrated a mean difference (95% CI) of 0.51 (-0.06 to 1.09) and 0.70 (0.07-1.34), respectively, for measurements made by TTEawake compared to TEEanesth. The percentage (95% CI) of paired measurements for e'lat and E/e'lat that lay outside the [-2, +2] study-specified boundary of acceptable agreement was 36% (27%-48%) and 39% (29%-51%), respectively. Results were generally robust to sensitivity analyses, including comparing measurements between TTEawake and TTEanesth, between TTEanesth and TEEanesth, and after regrading diastolic dysfunction by the American Society of Echocardiography (ASE)/European Association of CardioVascular Imaging (EACVI) algorithm. CONCLUSIONS: There was poor agreement between TTEawake and TEEanesth for grading diastolic dysfunction by a simplified algorithm, with disagreement by ≥1 grade in 54% and by ≥2 grades in 10% of the evaluable cohort. Future studies, including comparing the prognostic utility of TTEawake and TEEanesth for clinically important adverse outcomes that may be a consequence of diastolic dysfunction, are needed to understand whether this disagreement reflects random variability in Doppler variables, misclassification by the changed technique and physiological conditions of intraoperative TEE, or the accurate detection of a clinically relevant change in diastolic dysfunction.

Donor Lung Procurement by Surgical Fellow With an Expectation of High Rate of Lung Utilisation.

There is an ever increasing demand for donor lungs in patients waiting for transplantation. Lungs of many potential donors will be rejected if the standard criteria for donor assessment are followed. We have expanded our donor lung pool by accepting marginal donors and establishing a donation after circulatory death program. We have achieved comparable results using marginal donors and accepting donor lungs following donation after circulatory death. We present our assessment and technical guidelines on lung procurement taking into consideration an increasingly complex cohort of lung donors. These guidelines form the basis of the lung procurement training program involving surgical Fellows at the Alfred Hospital in Melbourne, Australia.

Substantial Increases Occur in Serum Activins and Follistatin during Lung Transplantation.

BACKGROUND: Lung transplantation exposes the donated lung to a period of anoxia. Re-establishing the circulation after ischemia stimulates inflammation causing organ damage. Since our published data established that activin A is a key pro-inflammatory cytokine, we assessed the roles of activin A and B, and their binding protein, follistatin, in patients undergoing lung transplantation. METHODS: Sera from 46 patients participating in a published study of remote ischemia conditioning in lung transplantation were used. Serum activin A and B, follistatin and 11 other cytokines were measured in samples taken immediately after anaesthesia induction, after remote ischemia conditioning or sham treatment undertaken just prior to allograft reperfusion and during the subsequent 24 hours. RESULTS: Substantial increases in serum activin A, B and follistatin occurred after the baseline sample, taken before anaesthesia induction and peaked immediately after the remote ischemia conditioning/sham treatment. The levels remained elevated 15 minutes after lung transplantation declining thereafter reaching baseline 2 hours post-transplant. Activin B and follistatin concentrations were lower in patients receiving remote ischemia conditioning compared to sham treated patients but the magnitude of the decrease did not correlate with early transplant outcomes. CONCLUSIONS: We propose that the increases in the serum activin A, B and follistatin result from a combination of factors; the acute phase response, the reperfusion response and the use of heparin-based anti-coagulants.

Intraoperative Transesophageal Echocardiography for the Evaluation and Management of Diastolic Dysfunction in Patients Undergoing Cardiac Surgery: A Survey of Current Practice.

OBJECTIVES: To characterize existing practice patterns for intraoperative evaluation and grading of diastolic dysfunction in patients undergoing cardiac surgery. DESIGN: A 14-question, multiple-choice survey of current practice for patients with diastolic dysfunction and the use of intraoperative transesophageal echocardiography (TEE) to evaluate, grade, and monitor changes in diastolic function. SETTING: Online survey. PARTICIPANTS: Members of the Society of Cardiovascular Anesthesiologists. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 515 respondents, there was a near-even spread between those based in an academic setting (53%) and those based in private practice (43%). Most respondents (81%) had completed training with certification in TEE. Most respondents (86%) currently modified their intraoperative management, at least some of the time, if they believed a patient was experiencing diastolic dysfunction, with 72% varying the nature of any modification according to the identified grade of diastolic dysfunction. Although 62% of respondents usually evaluated diastolic dysfunction in the pre-bypass period, only 59% of those evaluating diastolic dysfunction typically graded the dysfunction, with a variety of algorithms used for this purpose. The majority of respondents (62%) typically did not re-evaluate diastolic function using TEE in the post-bypass period. In 2 sample patients with Doppler data provided, there was marked variation in grading of diastolic dysfunction by respondents; this variation remained marked even within subgroups of respondents who typically used the same grading algorithm. CONCLUSIONS: Marked variation currently exists in how intraoperative TEE is used to evaluate, grade, and monitor diastolic function during cardiac surgery. This suggests clinically important knowledge gaps that should be addressed.

Safety, feasibility, and effect of remote ischemic conditioning in patients undergoing lung transplantation.

BACKGROUND: Primary graft dysfunction (PGD) remains a significant problem after lung transplantation. Data from animal and clinical studies suggest that remote ischemic conditioning (RIC) may reduce ischemia-reperfusion injury in solid organ transplantation. METHODS: A pilot randomized controlled trial of 60 patients undergoing bilateral sequential lung transplantation assessed the utility of RIC in attenuating PGD. Treated recipients underwent 3 cycles of lower limb ischemic conditioning before allograft reperfusion. The primary outcome measure was a comparison of the partial pressure of arterial oxygen/fraction of inspired oxygen ratio (P/F ratio) between treatment groups. RESULTS: No adverse effects of tourniquet application were observed. The mean lowest P/F ratio during the first 24 hours after transplantation was 271.3 mm Hg in the treatment arm vs 256.1 mm Hg in the control arm (p = 0.46). PGD grade and severity and the rate of acute rejection also showed a tendency to favor the treatment arm. Sub-group analysis demonstrated a significant benefit of treatment in patients with a primary diagnosis of restrictive lung disease, a group at high risk for the development of PGD. RIC was not accompanied by systemic release of high-molecular-weight group box 1. Levels of cytokines, high-molecular-weight group box 1, and endogenous secretory receptor for advanced glycation end products peaked within 2 hours after reperfusion and likely reflected donor organ quality rather than an effect of RIC. CONCLUSIONS: RIC did not significantly improve P/F ratios or PGD in this randomized controlled trial. However, encouraging results in this small study warrant a large multicenter trial of RIC in lung transplantation.

Carbon dioxide insufflation in open-chamber cardiac surgery: a double-blind, randomized clinical trial of neurocognitive effects.

OBJECTIVE: The aims of this study were first to analyze neurocognitive outcomes of patients after open-chamber cardiac surgery to determine whether carbon dioxide pericardial insufflation reduces incidence of neurocognitive decline (primary end point) as measured 6 weeks postoperatively and second to assess the utility of carbon dioxide insufflation in cardiac chamber deairing as assessed by transesophageal echocardiography. METHODS: A multicenter, prospective, double-blind, randomized, controlled trial compared neurocognitive outcomes in patients undergoing open-chamber (left-sided) cardiac surgery who were assigned carbon dioxide insufflation or placebo (control group) in addition to standardized mechanical deairing maneuvers. RESULTS: One hundred twenty-five patients underwent surgery and were randomly allocated. Neurocognitive testing showed no clinically significant differences in z scores between preoperative and postoperative testing. Linear regression was used to identify factors associated with neurocognitive decline. Factors most strongly associated with neurocognitive decline were hypercholesterolemia, aortic atheroma grade, and coronary artery disease. There was significantly more intracardiac gas noted on intraoperative transesophageal echocardiography in all cardiac chambers (left atrium, left ventricle, and aorta) at all measured times (after crossclamp removal, during weaning from cardiopulmonary bypass, and at declaration of adequate deairing by the anesthetist) in the control group than in the carbon dioxide group (P < .04). Deairing time was also significantly longer in the control group (12 minutes [interquartile range, 9-18] versus 9 minutes [interquartile range, 7-14 minutes]; P = .002). CONCLUSIONS: Carbon dioxide pericardial insufflation in open-chamber cardiac surgery does not affect postoperative neurocognitive decline. The most important factor is atheromatous vascular disease.